Comprehensive Physiology Wiley Online Library

Mechanobiology in Lung Epithelial Cells: Measurements, Perturbations, and Responses

Full Article on Wiley Online Library



Abstract

Epithelial cells of the lung are located at the interface between the environment and the organism and serve many important functions including barrier protection, fluid balance, clearance of particulate, initiation of immune responses, mucus and surfactant production, and repair following injury. Because of the complex structure of the lung and its cyclic deformation during the respiratory cycle, epithelial cells are exposed to continuously varying levels of mechanical stresses. While normal lung function is maintained under these conditions, changes in mechanical stresses can have profound effects on the function of epithelial cells and therefore the function of the organ. In this review, we will describe the types of stresses and strains in the lungs, how these are transmitted, and how these may vary in human disease or animal models. Many approaches have been developed to better understand how cells sense and respond to mechanical stresses, and we will discuss these approaches and how they have been used to study lung epithelial cells in culture. Understanding how cells sense and respond to changes in mechanical stresses will contribute to our understanding of the role of lung epithelial cells during normal function and development and how their function may change in diseases such as acute lung injury, asthma, emphysema, and fibrosis. © 2012 American Physiological Society. Compr Physiol 2:1‐29, 2012.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1.

Alveolar distension in lung inflation. An alveolus was imaged at baseline (Palv = 5 cmH2O, green pseudocolor) and hyperinflation (Palv = 20 cmH2O, red pseudocolor). Numbers in baseline image label two perimeter segments. An overlay of the images demonstrates inflation‐induced alveolar expansion, which increased perimeter length and alveolar diameter by 13% and 15%, respectively. Adapted (with permission) from reference 198.

Figure 2. Figure 2.

Diagram of pressures and forces acting on region of lung isolated by a plane transecting lung. A is the area of the transection and ΣFi is the sum of all tensile forces in the tissue elements transecting the plane. Adapted (with permission) from reference 170.

Figure 3. Figure 3.

Model of the disposition of axial, septal, and peripheral fibers in an acinus showing the effect of surface forces (arrows). From reference 285.

Reprinted with permission of the publisher. Copyright © 1984 by the President and Fellows of Harvard College.
Figure 4. Figure 4.

Force balance in the epithelial cell monolayer subjected to in‐plane stretch. Inward tension (red arrows) produced by active contractile tension generated by actomyosin motors and passive elastic recoil exerted by the actin meshwork is counterbalanced by outward adhesive forces (blue arrows) exerted by the adjacent cells and the extracellular matrix.

Figure 5. Figure 5.

Alveolar edema results in the expansion of the air‐filled alveolus and the contraction of the fluid‐filled alveolus. From reference 199.

Reprinted with permission of the American Thoracic Society. Copyright © American Thoracic Society.
Figure 6. Figure 6.

Measurement of cell mechanics with atomic force microscopy. (Top) The atomic force microscope indents the surface of the cell with a flexible cantilever with a sharp tip placed at its end. The cantilever is displaced with a piezoactuator. Force is computed from the lateral displacement on a segmented photodetector of a laser beam reflected on the cantilever. (Bottom) Force‐displacement (Fz) curve recorded in an alveolar epithelial cell showing the force measured while the cantilever was approached (solid line) toward the cell and retracted (dashed line) at constant velocity (6 μm/s). The curve exhibits hysteresis indicative of viscoelasticity. The retracted limb exhibits unspecific adhesion before the tip‐cell contact was lost (F < 0). The arrow indicates the estimated contact point. Sinusoidal oscillations were applied at a given indentation to compute the complex shear modulus.

Reprinted from reference 4 with permission from Elsevier.
Figure 7. Figure 7.

Magnetic twisting cytometry (MTC). (Top) Scanning electron microscopy of a bead bound to the surface of a human airway smooth muscle (HASM) cell. (Bottom) A magnetic field introduces a torque which causes the bead to rotate and to displace. M denotes the direction of the bead's magnetic moment.

Images reproduced (with permission) from reference 77.
Figure 8. Figure 8.

Optical tweezers. (A) A sketch of optical tweezers‐based cytorheometer. Optical tweezers were used to manipulate an intracellular granular structure (lamellar body, left circle), or an extracellular antibody coated glass bead (right circle). (B) A bright‐field image of lamellar bodies that abundantly exist in alveolar epithelial type II cells.

Reprinted (with permission) from reference 284.
Figure 9. Figure 9.

Mice myoblast stretched with microplates.

Reprinted from reference 60 with permission from Elsevier.
Figure 10. Figure 10.

Microaspiration of adhered cells. The micropipette is gently pressed against the glass slide and slid into contact with the adherent cell (A). A vacuum is applied; aspiration of the cell arrow into the pipette bore (B and C).

Reprinted from reference 32 with permission from Elsevier.
Figure 11. Figure 11.

Spontaneous displacement fluctuations of a microbead attached to the surface of human airway smooth muscle cells. Scale bar = 5 μm.

Reprinted (with permission) from reference 30.
Figure 12. Figure 12.

Measurements of cell tractions exerted to the substrate. (Top) Traction microscopy. Cell tractions exerted by a human airway smooth cell on a polyacrylamide gel coated with collagen. Colors show the magnitude and direction of the traction vectors in pascal. Adapted (with permission) from reference 31. (Bottom) Micropost array. Confocal image of immunofluorescence staining of a smooth muscle cell on posts. Position of fibronectin (red) on the tips of the posts was used to calculate force exerted by cells (white arrows).

Reprinted (with permission) from reference 242. Copyright (2003) National Academy of Sciences, USA.
Figure 13. Figure 13.

Uniaxial stretching device. A strip of silicone is held between the two clamps within the dish.

Reprinted from reference 178 with kind permission from Springer Science+Business Media.
Figure 14. Figure 14.

Cell stretcher based on the inflation of a clamped elastic diaphragm. Human epidermal keratinocytes (NHEKs) plated on a thin polydimethylsiloxane (PDMS) membrane are subjected to biaxial strain when subject to transdiaphragm pressure.

Reprinted from reference 225, Copyright (2007), with permission, from IOS Press.
Figure 15. Figure 15.

In‐plane biaxial cell membrane stretcher coupled to MTC. A flexible‐bottomed well is positioned on a sample holder based on a hollow cylindrical loading post, concentric with the objective of the microscope. The application of a negative pressure underneath the annular outer region of the sample results in a homogeneous and equibiaxial strain of the central area. Two pairs of coaxial coils are coupled to the stretching device to perform MTC. The pair transverse to the sample plane was used to magnetize the beads with a short and strong magnetic pulse. The pair coaxial to the optical axis applied oscillatory twisting fields. Adapted (with permission) from reference 257.

Figure 16. Figure 16.

Device to produce homogenous strains in a cruciform silicone membrane. Adapted (with permission) from reference 279.

Figure 17. Figure 17.

Biologically inspired design of a human breathing lung‐on‐a‐chip microdevice. Application of vacuum to the side chambers causes mechanical stretching of membrane forming the alveolar‐capillary barrier.

Adapted (with permission) from reference 127. Reprinted (with permission) from AAAS.
Figure 18. Figure 18.

Map of selected in vitro experiments utilizing alveolar epithelial cells, immortalized or primary. To distinguish the type of cells utilized in these studies, that is, AEII, A549, and AEI‐like, color coding is utilized as shown in the map. The AEI‐like cells are primary AEII cells that are cultured to four or more days. The reference numbers are given in the boxes and are listed in Table 1.

Figure 19. Figure 19.

Illustration indicating four ways in which the plasma membrane can respond to stretch. Adapted (with permission) from reference 267.

Figure 20. Figure 20.

Progression of an air bubble within the collapsed small airways results in large normal and shear stresses that deform the cells significantly and result in plasma membrane injury. Adapted (with permission) from reference 24.

Figure 21. Figure 21.

Frequency dependence of G′ (A) and G (B) under baseline conditions (filled symbols) and during application of a single stretch of 14.1% (open symbols). Data are plotted as means ± SEM. Adapted (with permission) from reference 257.

Figure 22. Figure 22.

Elastic modulus of cells is dependent on the distance from the wound edge in 16HBE cells. (A) Representative elastic modulus map of migrating 16HBE cells at a wound edge 2 h after wounding. Arrows indicate the wound edge as cells were migrating from right to left. Grey regions indicate plastic substrate. (B) Median elastic modulus values as a function of distance from the wound edge were summarized from four different fields. The dashed line indicates the median value from control cells far away from the wound edge (2.4 kPa), and the asterisks indicate a significant difference from this value (P < 0.05). Adapted (with permission) from reference 272.



Figure 1.

Alveolar distension in lung inflation. An alveolus was imaged at baseline (Palv = 5 cmH2O, green pseudocolor) and hyperinflation (Palv = 20 cmH2O, red pseudocolor). Numbers in baseline image label two perimeter segments. An overlay of the images demonstrates inflation‐induced alveolar expansion, which increased perimeter length and alveolar diameter by 13% and 15%, respectively. Adapted (with permission) from reference 198.



Figure 2.

Diagram of pressures and forces acting on region of lung isolated by a plane transecting lung. A is the area of the transection and ΣFi is the sum of all tensile forces in the tissue elements transecting the plane. Adapted (with permission) from reference 170.



Figure 3.

Model of the disposition of axial, septal, and peripheral fibers in an acinus showing the effect of surface forces (arrows). From reference 285.

Reprinted with permission of the publisher. Copyright © 1984 by the President and Fellows of Harvard College.


Figure 4.

Force balance in the epithelial cell monolayer subjected to in‐plane stretch. Inward tension (red arrows) produced by active contractile tension generated by actomyosin motors and passive elastic recoil exerted by the actin meshwork is counterbalanced by outward adhesive forces (blue arrows) exerted by the adjacent cells and the extracellular matrix.



Figure 5.

Alveolar edema results in the expansion of the air‐filled alveolus and the contraction of the fluid‐filled alveolus. From reference 199.

Reprinted with permission of the American Thoracic Society. Copyright © American Thoracic Society.


Figure 6.

Measurement of cell mechanics with atomic force microscopy. (Top) The atomic force microscope indents the surface of the cell with a flexible cantilever with a sharp tip placed at its end. The cantilever is displaced with a piezoactuator. Force is computed from the lateral displacement on a segmented photodetector of a laser beam reflected on the cantilever. (Bottom) Force‐displacement (Fz) curve recorded in an alveolar epithelial cell showing the force measured while the cantilever was approached (solid line) toward the cell and retracted (dashed line) at constant velocity (6 μm/s). The curve exhibits hysteresis indicative of viscoelasticity. The retracted limb exhibits unspecific adhesion before the tip‐cell contact was lost (F < 0). The arrow indicates the estimated contact point. Sinusoidal oscillations were applied at a given indentation to compute the complex shear modulus.

Reprinted from reference 4 with permission from Elsevier.


Figure 7.

Magnetic twisting cytometry (MTC). (Top) Scanning electron microscopy of a bead bound to the surface of a human airway smooth muscle (HASM) cell. (Bottom) A magnetic field introduces a torque which causes the bead to rotate and to displace. M denotes the direction of the bead's magnetic moment.

Images reproduced (with permission) from reference 77.


Figure 8.

Optical tweezers. (A) A sketch of optical tweezers‐based cytorheometer. Optical tweezers were used to manipulate an intracellular granular structure (lamellar body, left circle), or an extracellular antibody coated glass bead (right circle). (B) A bright‐field image of lamellar bodies that abundantly exist in alveolar epithelial type II cells.

Reprinted (with permission) from reference 284.


Figure 9.

Mice myoblast stretched with microplates.

Reprinted from reference 60 with permission from Elsevier.


Figure 10.

Microaspiration of adhered cells. The micropipette is gently pressed against the glass slide and slid into contact with the adherent cell (A). A vacuum is applied; aspiration of the cell arrow into the pipette bore (B and C).

Reprinted from reference 32 with permission from Elsevier.


Figure 11.

Spontaneous displacement fluctuations of a microbead attached to the surface of human airway smooth muscle cells. Scale bar = 5 μm.

Reprinted (with permission) from reference 30.


Figure 12.

Measurements of cell tractions exerted to the substrate. (Top) Traction microscopy. Cell tractions exerted by a human airway smooth cell on a polyacrylamide gel coated with collagen. Colors show the magnitude and direction of the traction vectors in pascal. Adapted (with permission) from reference 31. (Bottom) Micropost array. Confocal image of immunofluorescence staining of a smooth muscle cell on posts. Position of fibronectin (red) on the tips of the posts was used to calculate force exerted by cells (white arrows).

Reprinted (with permission) from reference 242. Copyright (2003) National Academy of Sciences, USA.


Figure 13.

Uniaxial stretching device. A strip of silicone is held between the two clamps within the dish.

Reprinted from reference 178 with kind permission from Springer Science+Business Media.


Figure 14.

Cell stretcher based on the inflation of a clamped elastic diaphragm. Human epidermal keratinocytes (NHEKs) plated on a thin polydimethylsiloxane (PDMS) membrane are subjected to biaxial strain when subject to transdiaphragm pressure.

Reprinted from reference 225, Copyright (2007), with permission, from IOS Press.


Figure 15.

In‐plane biaxial cell membrane stretcher coupled to MTC. A flexible‐bottomed well is positioned on a sample holder based on a hollow cylindrical loading post, concentric with the objective of the microscope. The application of a negative pressure underneath the annular outer region of the sample results in a homogeneous and equibiaxial strain of the central area. Two pairs of coaxial coils are coupled to the stretching device to perform MTC. The pair transverse to the sample plane was used to magnetize the beads with a short and strong magnetic pulse. The pair coaxial to the optical axis applied oscillatory twisting fields. Adapted (with permission) from reference 257.



Figure 16.

Device to produce homogenous strains in a cruciform silicone membrane. Adapted (with permission) from reference 279.



Figure 17.

Biologically inspired design of a human breathing lung‐on‐a‐chip microdevice. Application of vacuum to the side chambers causes mechanical stretching of membrane forming the alveolar‐capillary barrier.

Adapted (with permission) from reference 127. Reprinted (with permission) from AAAS.


Figure 18.

Map of selected in vitro experiments utilizing alveolar epithelial cells, immortalized or primary. To distinguish the type of cells utilized in these studies, that is, AEII, A549, and AEI‐like, color coding is utilized as shown in the map. The AEI‐like cells are primary AEII cells that are cultured to four or more days. The reference numbers are given in the boxes and are listed in Table 1.



Figure 19.

Illustration indicating four ways in which the plasma membrane can respond to stretch. Adapted (with permission) from reference 267.



Figure 20.

Progression of an air bubble within the collapsed small airways results in large normal and shear stresses that deform the cells significantly and result in plasma membrane injury. Adapted (with permission) from reference 24.



Figure 21.

Frequency dependence of G′ (A) and G (B) under baseline conditions (filled symbols) and during application of a single stretch of 14.1% (open symbols). Data are plotted as means ± SEM. Adapted (with permission) from reference 257.



Figure 22.

Elastic modulus of cells is dependent on the distance from the wound edge in 16HBE cells. (A) Representative elastic modulus map of migrating 16HBE cells at a wound edge 2 h after wounding. Arrows indicate the wound edge as cells were migrating from right to left. Grey regions indicate plastic substrate. (B) Median elastic modulus values as a function of distance from the wound edge were summarized from four different fields. The dashed line indicates the median value from control cells far away from the wound edge (2.4 kPa), and the asterisks indicate a significant difference from this value (P < 0.05). Adapted (with permission) from reference 272.

References
 1. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The acute respiratory distress syndrome network. N Engl J Med 342: 1301‐1308, 2000.
 2. Adkins WK, Hernandez LA, Coker PJ, Buchanan B, Parker JC. Age effects susceptibility to pulmonary barotrauma in rabbits. Crit Care Med 19: 390‐393, 1991.
 3. Agostoni E, Hyatt RE. Static behaviour of the respiratory system. In: Macklem PT, Mead J, editors. Handbook of Physiology. Mechanics of Breathing. Bethesda, MD: American Physiological Society, 1986, sect. 3, pt. 1, p. 113‐130.
 4. Alcaraz J, Buscemi L, Grabulosa M, Trepat X, Fabry B, Farre R, Navajas D. Microrheology of human lung epithelial cells measured by atomic force microscopy. Biophys J 84: 2071‐2079, 2003.
 5. Alcaraz J, Buscemi L, Puig‐de‐Morales M, Colchero J, Baro A, Navajas D. Correction of microrheological measurements of soft samples with atomic force microscopy for the hydrodynamic drag on the cantilever. Langmuir 18: 716‐721, 2002.
 6. Alcorn D, Adamson TM, Lambert TF, Maloney JE, Ritchie BC, Robinson PM. Morphological effects of chronic tracheal ligation and drainage in the fetal lamb lung. J Anat 123: 649‐660, 1977.
 7. An SS, Bai TR, Bates JH, Black JL, Brown RH, Brusasco V, Chitano P, Deng L, Dowell M, Eidelman DH, Fabry B, Fairbank NJ, Ford LE, Fredberg JJ, Gerthoffer WT, Gilbert SH, Gosens R, Gunst SJ, Halayko AJ, Ingram RH, Irvin CG, James AL, Janssen LJ, King GG, Knight DA, Lauzon AM, Lakser OJ, Ludwig MS, Lutchen KR, Maksym GN, Martin JG, Mauad T, McParland BE, Mijailovich SM, Mitchell HW, Mitchell RW, Mitzner W, Murphy TM, Pare PD, Pellegrino R, Sanderson MJ, Schellenberg RR, Seow CY, Silveira PS, Smith PG, Solway J, Stephens NL, Sterk PJ, Stewart AG, Tang DD, Tepper RS, Tran T, Wang L. Airway smooth muscle dynamics: A common pathway of airway obstruction in asthma. Eur Respir J 29: 834‐860, 2007.
 8. Arold SP, Bartolák‐Suki E, Suki B. Variable stretch pattern enhances surfactant secretion in alveolar type II cells in culture. Am J Physiol Lung Cell Mol Physiol 296: L574‐L581, 2009.
 9. Arold SP, Wong JY, Suki B. Design of a new stretching apparatus and the effects of cyclic strain and substratum on mouse lung epithelial‐12 cells. Ann Biomed Eng 35: 1156‐1164, 2007.
 10. Ashkin A, Dziedzic JM, Yamane T. Optical trapping and manipulation of single cells using infrared laser beams. Nature 330: 769‐771, 1987.
 11. Azeloglu EU, Bhattacharya J, Costa KD. Atomic force microscope elastography reveals phenotypic differences in alveolar cell stiffness. J Appl Physiol 105: 652‐661, 2008.
 12. Bachofen H, Schurch S, Urbinelli M, Weibel ER. Relations among alveolar surface tension, surface area, volume, and recoil pressure. J Appl Physiol 62: 1878‐1887, 1987.
 13. Bajaj P, Tang X, Saif TA, Bashir R. Stiffness of the substrate influences the phenotype of embryonic chicken cardiac myocytes. J Biomed Mater Res A 95: 1261‐1269, 2010.
 14. Banes AJ, Gilbert J, Taylor D, Monbureau O. A new vacuum‐operated stress‐providing instrument that applies static or variable duration cyclic tension or compression to cells in vitro. J Cell Sci 75: 35‐42, 1985.
 15. Barnes PJ. Medical progress: Chronic obstructive pulmonary disease. New Engl J Med 343: 269‐280, 2000.
 16. Bates JHT, Davis GS, Majumdar A, Butnor KJ, Suki B. Linking parenchymal disease progression to changes in lung mechanical function by percolation. Am J Respir Crit Care Med 176: 617‐623, 2007.
 17. Bausch AR, Moller W, Sackmann E. Measurement of local viscoelasticity and forces in living cells by magnetic tweezers. Biophys J 76: 573‐579, 1999.
 18. Bausch AR, Ziemann F, Boulbitch AA, Jacobson K, Sackmann E. Local measurements of viscoelastic parameters of adherent cell surfaces by magnetic bead microrheometry. Biophys J 75: 2038‐2049, 1998.
 19. Benachi A, Delezoide AL, Chailley‐Heu B, Preece M, Bourbon JR, Ryder T. Ultrastructural evaluation of lung maturation in a sheep model of diaphragmatic hernia and tracheal occlusion. Am J Respir Cell Mol Biol 20: 805‐812, 1999.
 20. Benoit M, Gabriel D, Gerisch G, Gaub HE. Discrete interactions in cell adhesion measured by single‐molecule force spectroscopy. Nat Cell Biol 2: 313‐317, 2000.
 21. Bensadoun ES, Burke AK, Hogg JC, Roberts CR. Proteoglycan deposition in pulmonary fibrosis. Am J Respir Crit Care Med 154: 1819‐1828, 1996.
 22. Bhana B, Iyer RK, Chen WL, Zhao R, Sider KL, Likhitpanichkul M, Simmons CA, Radisic M. Influence of substrate stiffness on the phenotype of heart cells. Biotechnol Bioeng 105: 1148‐1160, 2010.
 23. Bieler FH, Ott CE, Thompson MS, Seidel R, Ahrens S, Epari DR, Wilkening U, Schaser KD, Mundlos S, Duda GN. Biaxial cell stimulation: A mechanical validation. J Biomech 42: 1692‐1696, 2009.
 24. Bilek AM, Dee KC, Gaver DP, 3rd. Mechanisms of surface‐tension‐induced epithelial cell damage in a model of pulmonary airway reopening. J Appl Physiol 94: 770‐783, 2003.
 25. Bilodeau GG. Regular pyramid punch problem. J Appl Mech 59: 519‐523, 1992.
 26. Binnig G, Quate CF, Gerber C. Atomic force microscope. Phys Rev Lett 56: 930‐933, 1986.
 27. Brody JS, Burki R, Kaplan N. Deoxyribonucleic acid synthesis in lung cells during compensatory lung growth after pneumonectomy. Am Rev Respir Dis 117: 307‐316, 1978.
 28. Budinger GR, Urich D, DeBiase PJ, Chiarella SE, Burgess ZO, Baker CM, Soberanes S, Mutlu GM, Jones JC. Stretch‐induced activation of AMP kinase in the lung requires dystroglycan. Am J Respir Cell Mol Biol 39: 666‐672, 2008.
 29. Buhain WJ, Brody JS. Compensatory growth of the lung following pneumonectomy. J Appl Physiol 35: 898‐902, 1973.
 30. Bursac P, Lenormand G, Fabry B, Oliver M, Weitz DA, Viasnoff V, Butler JP, Fredberg JJ. Cytoskeletal remodelling and slow dynamics in the living cell. Nat Mater 4: 557‐561, 2005.
 31. Butler JP, Tolic‐Norrelykke IM, Fabry B, Fredberg JJ. Traction fields, moments, and strain energy that cells exert on their surroundings. Am J Physiol Cell Physiol 282: C595‐C605, 2002.
 32. Byfield FJ, Reen RK, Shentu TP, Levitan I, Gooch KJ. Endothelial actin and cell stiffness is modulated by substrate stiffness in 2D and 3D. J Biomech 42: 1114‐1119, 2009.
 33. Caille N, Tardy Y, Meister JJ. Assessment of strain field in endothelial cells subjected to uniaxial deformation of their substrate. Ann Biomed Eng 26: 409‐416, 1998.
 34. Carlton DP, Cummings JJ, Scheerer RG, Poulain FR, Bland RD. Lung overexpansion increases pulmonary microvascular protein permeability in young lambs. J Appl Physiol 69: 577‐583, 1990.
 35. Carney DE, Bredenberg CE, Schiller HJ, Picone AL, McCann UG, Gatto LA, Bailey G, Fillinger M, Nieman GF. The mechanism of lung volume change during mechanical ventilation. Am J Respir Crit Care Med 160: 1697‐1702, 1999.
 36. Cavanaugh KJ, Cohen TS, Margulies SS. Stretch increases alveolar epithelial permeability to uncharged micromolecules. Am J Physiol Cell Physiol 290: C1179‐C1188, 2006.
 37. Cavanaugh KJ, Jr., Oswari J, Margulies SS. Role of stretch on tight junction structure in alveolar epithelial cells. Am J Respir Cell Mol Biol 25: 584‐591, 2001.
 38. Chapman KE, Sinclair SE, Zhuang D, Hassid A, Desai LP, Waters CM. Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 289: L834‐L841, 2005.
 39. Chaudhuri O, Parekh SH, Fletcher DA. Reversible stress softening of actin networks. Nature 445: 295‐298, 2007.
 40. Chaudhuri O, Parekh SH, Lam WA, Fletcher DA. Combined atomic force microscopy and side‐view optical imaging for mechanical studies of cells. Nat Meth 6: 383‐387, 2009.
 41. Chetta A, Foresi A, Del Donno M, Consigli GF, Bertorelli G, Pesci A, Barbee RA, Olivieri D. Bronchial responsiveness to distilled water and methacholine and its relationship to inflammation and remodeling of the airways in asthma. Am J Respir Crit Care Med 153: 910‐917, 1996.
 42. Chu EK, Cheng J, Foley JS, Mecham BH, Owen CA, Haley KJ, Mariani TJ, Kohane IS, Tschumperlin DJ, Drazen JM. Induction of the plasminogen activator system by mechanical stimulation of human bronchial epithelial cells. Am J Respir Cell Mol Biol 35: 628‐638, 2006.
 43. Cohen TS, Cavanaugh KJ, Margulies SS. Frequency and peak stretch magnitude affect alveolar epithelial permeability. Eur Respir J 32: 854‐861, 2008.
 44. Cohen TS, Gray Lawrence G, Khasgiwala A, Margulies SS. MAPK activation modulates permeability of isolated rat alveolar epithelial cell monolayers following cyclic stretch. PLoS One 5: e10385, 2010.
 45. Cohn R. Factors affecting the postnatal growth of the lung. Anat Rec 75: 195‐205, 1938.
 46. Copland IB, Kavanagh BP, Engelberts D, McKerlie C, Belik J, Post M. Early changes in lung gene expression due to high tidal volume. Am J Respir Crit Care Med 168: 1051‐1059, 2003.
 47. Copland IB, Post M. Stretch‐activated signaling pathways responsible for early response gene expression in fetal lung epithelial cells. J Cell Physiol 210: 133‐143, 2007.
 48. Crick FHC, Hughes AFW. The physical properties of cytoplasm: A study by means of the magnetic particle method. 1. Experimental. Exp Cell Res 1: 37‐80, 1950.
 49. Crocker JC, Valentine MT, Weeks ER, Gisler T, Kaplan PD, Yodh AG, Weitz DA. Two‐point microrheology of inhomogeneous soft materials. Phys Rev Lett 85: 888‐891, 2000.
 50. Crosby LM, Waters CM. Epithelial repair mechanisms in the lung. Am J Physiol Lung Cell Mol Physiol 298: L715‐L731, 2010.
 51. Danto SI, Shannon JM, Borok Z, Zabski SM, Crandall ED. Reversible transdifferentiation of alveolar epithelial cells. Am J Respir Cell Mol Biol 12: 497‐502, 1995.
 52. Davies DE. The role of the epithelium in airway remodeling in asthma. Proc Am Thorac Soc 6: 678‐682, 2009.
 53. Dembo M, Oliver T, Ishihara A, Jacobson K. Imaging the traction stresses exerted by locomoting cells with the elastic substratum method. Biophys J 70: 2008‐2022, 1996.
 54. Dembo M, Wang YL. Stresses at the cell‐to‐substrate interface during locomotion of fibroblasts. Biophys J 76: 2307‐2316, 1999.
 55. Desai LP, Aryal AM, Ceacareanu B, Hassid A, Waters CM. RhoA and Rac1 are both required for efficient wound closure of airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 287: L1134‐L1144, 2004.
 56. Desai LP, Chapman KE, Waters CM. Mechanical stretch decreases migration of alveolar epithelial cells through mechanisms involving Rac1 and Tiam1. Am J Physiol Lung Cell Mol Physiol 295: L958‐L965, 2008.
 57. Desai LP, White SR, Waters CM. Mechanical stretch decreases FAK phosphorylation and reduces cell migration through loss of JIP3‐induced JNK phosphorylation in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 297: L520‐L529, 2009.
 58. Desai LP, White SR, Waters CM. Cyclic mechanical stretch decreases cell migration by inhibiting phosphatidylinositol 3‐kinase‐ and focal adhesion kinase‐mediated JNK1 activation. J Biol Chem 285: 4511‐4519, 2010.
 59. Desprat N, Richert A, Simeon J, Asnacios A. Creep function of a single living cell. Biophys J 88: 2224‐2233, 2005.
 60. DiPaolo BC, Lenormand G, Fredberg JJ, Margulies SS. Stretch magnitude and frequency‐dependent actin cytoskeleton remodeling in alveolar epithelia. Am J Physiol Cell Physiol 299: C345‐C353, 2010.
 61. Dolhnikoff M, Mauad T, Ludwig MS. Extracellular matrix and oscillatory mechanics of rat lung parenchyma in bleomycin‐induced fibrosis. Am J Respir Crit Care Med 160: 1750‐1757, 1999.
 62. Dong C, Skalak R, Sung KLP, Schmidschonbein GW, Chien S. Passive deformation analysis of human‐leukocytes. J Biomech Eng 110: 27‐36, 1988.
 63. dos Santos CC, Han B, Andrade CF, Bai X, Uhlig S, Hubmayr R, Tsang M, Lodyga M, Keshavjee S, Slutsky AS, Liu M. DNA microarray analysis of gene expression in alveolar epithelial cells in response to TNFalpha, LPS, and cyclic stretch. Physiol Genomics 19: 331‐342, 2004.
 64. dos Santos CC, Slutsky AS. Invited review: mechanisms of ventilator‐induced lung injury: A perspective. J Appl Physiol 89: 1645‐1655, 2000.
 65. dos Santos CC, Slutsky AS. The contribution of biophysical lung injury to the development of biotrauma. Annu Rev Physiol 68: 585‐618, 2006.
 66. Dreyfuss D, Saumon G. Barotrauma is volutrauma, but which volume is the one responsible? Intensive Care Med 18: 139‐141, 1992.
 67. Dreyfuss D, Saumon G. Ventilator‐induced lung injury: Lessons from experimental studies. Am J Respir Crit Care Med 157: 294‐323, 1998.
 68. Dreyfuss D, Soler P, Basset G, Saumon G. High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end‐expiratory pressure. Am Rev Respir Dis 137: 1159‐1164, 1988.
 69. du Roure O, Saez A, Buguin A, Austin RH, Chavrier P, Siberzan P, Ladoux B. Force mapping in epithelial cell migration. Proc Natl Acad Sci U S A 102: 2390‐2395, 2005.
 70. Dudek SM, Garcia JGN. Cytoskeletan regulation of pulmonary vascular permeability. J Appl Physiol 91: 1487‐1500, 2001.
 71. Dupuit F, Gaillard D, Hinnrasky J, Mongodin E, de Bentzmann S, Copreni E, Puchelle E. Differentiated and functional human airway epithelium regeneration in tracheal xenografts. Am J Physiol Lung Cell Mol Physiol 278: L165‐L176, 2000.
 72. Edwards YS, Sutherland LM, Power JH, Nicholas TE, Murray AW. Cyclic stretch induces both apoptosis and secretion in rat alveolar type II cells. FEBS Lett 448: 127‐130, 1999.
 73. Erjefalt JS, Erjefalt I, Sundler F, Persson CG. Microcirculation‐derived factors in airway epithelial repair in vivo. Microvasc Res 48: 161‐178, 1994.
 74. Erjefalt JS, Erjefalt I, Sundler F, Persson CG. Effects of topical budesonide on epithelial restitution in vivo in guinea pig trachea. Thorax 50: 785‐792, 1995a.
 75. Erjefalt JS, Erjefalt I, Sundler F, Persson CG. In vivo restitution of airway epithelium. Cell Tissue Res 281: 305‐316, 1995b.
 76. Fabry B, Maksym GN, Butler JP, Glogauer M, Navajas D, Fredberg JJ. Scaling the microrheology of living cells. Phys Rev Lett 87: 148102, 2001.
 77. Faridy EE, Permutt S, Riley RL. Effect of ventilation on surface forces in excised dogs’ lungs. J Appl Physiol 21: 1453‐1462, 1966.
 78. Fehrenbach H, Voswinckel R, Michl V, Mehling T, Fehrenbach A, Seeger W, Nyengaard JR. Neoalveolarisation contributes to compensatory lung growth following pneumonectomy in mice. Eur Respir J 31: 515‐522, 2008.
 79. Felder E, Siebenbrunner M, Busch T, Fois G, Miklavc P, Walther P, Dietl P. Mechanical strain of alveolar type II cells in culture: Changes in the transcellular cytokeratin network and adaptations. Am J Physiol Lung Cell Mol Physiol 295: L849‐L857, 2008.
 80. Felsenfeld DP, Schwartzberg PL, Venegas A, Tse R, Sheetz MP. Selective regulation of integrin–cytoskeleton interactions by the tyrosine kinase Src. Nat Cell Biol 1: 200‐206, 1999.
 81. Fenteany G, Janmey PA, Stossel TP. Signaling pathways and cell mechanics involved in wound closure by epithelial cell sheets. Curr Biol 10: 831‐838, 2000.
 82. Fernandez P, Pullarkat PA, Ott A. A master relation defines the nonlinear viscoelasticity of single fibroblasts. Biophys J 90: 3796‐3805, 2006.
 83. Fisher JL, Levitan I, Margulies SS. Plasma membrane surface increases with tonic stretch of alveolar epithelial cells. Am J Respir Cell Mol Biol 31: 200‐208, 2004.
 84. Fisher JL, Margulies SS. Na(+)‐K(+)‐ATPase activity in alveolar epithelial cells increases with cyclic stretch. Am J Physiol Lung Cell Mol Physiol 283: L737‐L746, 2002.
 85. Flecknoe S, Harding R, Maritz G, Hooper SB. Increased lung expansion alters the proportions of type I and type II alveolar epithelial cells in fetal sheep. Am J Physiol Lung Cell Mol Physiol 278: L1180‐L1185, 2000.
 86. Flecknoe SJ, Wallace MJ, Cock ML, Harding R, Hooper SB. Changes in alveolar epithelial cell proportions during fetal and postnatal development in sheep. Am J Physiol Lung Cell Mol Physiol 285: L664‐L670, 2003.
 87. Flecknoe SJ, Wallace MJ, Harding R, Hooper SB. Determination of alveolar epithelial cell phenotypes in fetal sheep: Evidence for the involvement of basal lung expansion. J Physiol 542: 245‐253, 2002.
 88. Frank JA, Gutierrez JA, Jones KD, Allen L, Dobbs L, Matthay MA. Low tidal volume reduces epithelial and endothelial injury in acid‐injured rat lungs. Am J Respir Crit Care Med 165: 242‐249, 2002.
 89. Frank JA, Matthay MA. Science review: Mechanisms of ventilator‐induced injury. Crit Care 7: 233‐241, 2003.
 90. Fredberg JJ. Airway smooth muscle in asthma: Flirting with disaster. Eur Respir J 12: 1252‐1256, 1998.
 91. Fredberg JJ, Inouye D, Miller B, Nathan M, Jafari S, Raboudi SH, Butler JP, Shore SA. Airway smooth muscle, tidal stretches, and dynamically determined contractile states. Am J Respir Crit Care Med 156: 1752‐1759, 1997.
 92. Fredberg JJ, Kamm RD. Stress Transmission in the lung: Pathways from organ to molecule. Annu Rev Physiol 68: 507‐541, 2006.
 93. Frick M, Bertocchi C, Jennings P, Haller T, Mair N, Singer W, Pfaller W, Ritsch‐Marte M, Dietl P. Ca2+ entry is essential for cell strain‐induced lamellar body fusion in isolated rat type II pneumocytes. Am J Physiol Lung Cell Mol Physiol 286: L210‐L220, 2004.
 94. Fung YC. Biomechanics. Mechanical Properties of Living Tissues (2nd ed). New York, NY: Springer‐Verlag, 1993.
 95. Gajic O, Lee J, Doerr CH, Berrios JC, Myers JL, Hubmayr RD. Ventilator‐induced cell wounding and repair in the intact lung. Am J Respir Crit Care Med 167: 1057‐1063, 2003.
 96. Gattinoni L, Caironi P, Carlesso E. How to ventilate patients with acute lung injury and acute respiratory distress syndrome. Curr Opin Crit Care 11: 69‐76, 2005.
 97. Gavara N, Roca‐Cusachs P, Sunyer R, Farre R, Navajas D. Mapping cell‐matrix stresses during stretch reveals inelastic reorganization of the cytoskeleton. Biophys J 95: 464‐471, 2008.
 98. Geiger RC, Kaufman CD, Lam AP, Budinger GR, Dean DA. Tubulin acetylation and histone deacetylase 6 activity in the lung under cyclic load. Am J Respir Cell Mol Biol 40: 76‐82, 2009.
 99. Geiger RC, Taylor W, Glucksberg MR, Dean DA. Cyclic stretch‐induced reorganization of the cytoskeleton and its role in enhanced gene transfer. Gene Ther 13: 725‐731, 2006.
 100. Gerstmair A, Fois G, Innerbichler S, Dietl P, Felder E. A device for simultaneous live cell imaging during uni‐axial mechanical strain or compression. J Appl Physiol 107: 613‐620, 2009.
 101. Ghadiali SN, Gaver DP. Biomechanics of liquid‐epithelium interactions in pulmonary airways. Respir Physiol Neurobiol 163: 232‐243, 2008.
 102. Gil J, Bachofen H, Gehr P, Weibel ER. Alveolar volume‐surface area relation in air‐ and saline‐filled lungs fixed by vascular perfusion. J Appl Physiol 47: 990‐1001, 1979.
 103. Gil J, Weibel ER. Morphological study of pressure‐volume hysteresis in rat lungs fixed by vascular perfusion. Respir Physiol 15: 190‐213, 1972.
 104. Gunst SJ, Tang DD. The contractile apparatus and mechanical properties of airway smooth muscle. Eur Respir J 15: 600‐616, 2000.
 105. Hammerschmidt S, Kuhn H, Gessner C, Seyfarth HJ, Wirtz H. Stretch‐induced alveolar type II cell apoptosis: role of endogenous bradykinin and PI3K‐Akt signaling. Am J Respir Cell Mol Biol 37: 699‐705, 2007.
 106. Hammerschmidt S, Kuhn H, Grasenack T, Gessner C, Wirtz H. Apoptosis and necrosis induced by cyclic mechanical stretching in alveolar type II cells. Am J Respir Cell Mol Biol 30: 396‐402, 2004.
 107. Hammerschmidt S, Kuhn H, Sack U, Schlenska A, Gessner C, Gillissen A, Wirtz H. Mechanical stretch alters alveolar type II cell mediator release toward a proinflammatory pattern. Am J Respir Cell Mol Biol 33: 203‐210, 2005.
 108. Han B, Lodyga M, Liu M. Ventilator‐induced lung injury: Role of protein‐protein interaction in mechanosensation. Proc Am Thorac Soc 2: 181‐187, 2005.
 109. Harding R, Hooper SB. Regulation of lung expansion and lung growth before birth. J Appl Physiol 81: 209‐224, 1996.
 110. Henon S, Lenormand G, Richert A, Gallet F. A new determination of the shear modulus of the human erythrocyte membrane using optical tweezers. Biophys J 76: 1145‐1151, 1999.
 111. Hernandez LA, Peevy KJ, Moise AA, Parker JC. Chest wall restriction limits high airway pressure‐induced lung injury in young rabbits. J Appl Physiol 66: 2364‐2368, 1989.
 112. Hochmuth RM. Micropipette aspiration of living cells. J Biomech 33: 15‐22, 2000.
 113. Hoffman AM, Shifren A, Mazan MR, Gruntman AM, Lascola KM, Nolen‐Walston RD, Kim CF, Tsai L, Pierce RA, Mecham RP, Ingenito EP. Matrix modulation of compensatory lung regrowth and progenitor cell proliferation in mice. Am J Physiol Lung Cell Mol Physiol 298: L158‐L168, 2010.
 114. Hoffman BD, Massiera G, Van Citters KM, Crocker JC. The consensus mechanics of cultured mammalian cells. Proc Natl Acad Sci U S A 103: 10259‐10264, 2006.
 115. Hoh JH, Schoenenberger CA. Surface‐morphology and mechanical‐properties of Mdck monolayers by atomic‐force microscopy. J Cell Sci 107: 1105‐1114, 1994.
 116. Holgate ST, Lackie P, Wilson S, Roche W, Davies D. Bronchial epithelium as a key regulator of airway allergen sensitization and remodeling in asthma. Am J Respir Crit Care Med 162: S113‐S117, 2000.
 117. Hooper SB, Han VK, Harding R. Changes in lung expansion alter pulmonary DNA synthesis and IGF‐II gene expression in fetal sheep. Am J Physiol 265: L403‐L409, 1993.
 118. Hooper SB, Wallace MJ. Role of the physicochemical environment in lung development. Clin Exp Pharmacol Physiol 33: 273‐279, 2006.
 119. Horiba K, Fukuda Y. Synchronous appearance of fibronectin, integrin alpha 5 beta 1, vinculin and actin in epithelial cells and fibroblasts during rat tracheal wound healing. Virchows Archiv 425: 425‐434, 1994.
 120. Hsia CC. Signals and mechanisms of compensatory lung growth. J Appl Physiol 97: 1992‐1998, 2004.
 121. Huang L, Mathieu PS, Helmke BP. A stretching device for high‐resolution live‐cell imaging. Ann Biomed Eng 38: 1728‐1740, 2010.
 122. Hubmayr RD. Perspective on lung injury and recruitment: A skeptical look at the opening and collapse story. Am J Respir Crit Care Med 165: 1647‐1653, 2002.
 123. Hughes JM, Hoppin FG, Jr., Mead J. Effect of lung inflation on bronchial length and diameter in excised lungs. J Appl Physiology 32: 25‐35, 1972.
 124. Huh D, Fujioka H, Tung YC, Futai N, Paine R, 3rd, Grotberg JB, Takayama S. Acoustically detectable cellular‐level lung injury induced by fluid mechanical stresses in microfluidic airway systems. Proc Natl Acad Sci U S A 104: 18886‐18891, 2007.
 125. Huh D, Matthews BD, Mammoto A, Montoya‐Zavala M, Hsin HY, Ingber DE. Reconstituting organ‐level lung functions on a chip. Science 328: 1662‐1668, 2010.
 126. Hung CT, Williams JL. A method for inducing equi‐biaxial and uniform strains in elastomeric membranes used as cell substrates. J Biomech 27: 227‐232, 1994.
 127. Jafari B, Ouyang B, Li LF, Hales CA, Quinn DA. Intracellular glutathione in stretch‐induced cytokine release from alveolar type‐2 like cells. Respirology 9: 43‐53, 2004.
 128. Jonas M, Huang H, Kamm RD, So PTC. Fast fluorescence laser tracking microrheometry, I: Instrument development. Biophys J 94: 1459‐1469, 2008.
 129. Jones JC, Lane K, Hopkinson SB, Lecuona E, Geiger RC, Dean DA, Correa‐Meyer E, Gonzales M, Campbell K, Sznajder JI, Budinger S. Laminin‐6 assembles into multimolecular fibrillar complexes with perlecan and participates in mechanical‐signal transduction via a dystroglycan‐dependent, integrin‐independent mechanism. J Cell Sci 118: 2557‐2566, 2005.
 130. Kamgoue A, Ohayon J, Tracqui P. Estimation of cell Young's modulus of adherent cells probed by optical and magnetic tweezers: Influence of cell thickness and bead immersion. J Biomech Eng 129: 523‐530, 2007.
 131. Kaverina I, Krylyshkina O, Beningo K, Anderson K, Wang YL, Small JV. Tensile stress stimulates microtubule outgrowth in living cells. J Cell Sci 115: 2283‐2291, 2002.
 132. Kaverina I, Krylyshkina O, Small JV. Regulation of substrate adhesion dynamics during cell motility. Int J Biochem Cell Biol 34: 746‐761, 2002.
 133. Kay SS, Bilek AM, Dee KC, Gaver DP, 3rd. Pressure gradient, not exposure duration, determines the extent of epithelial cell damage in a model of pulmonary airway reopening. J Appl Physiol 97: 269‐276, 2004.
 134. Khatiwala CB, Peyton SR, Putnam AJ. Intrinsic mechanical properties of the extracellular matrix affect the behavior of pre‐osteoblastic MC3T3‐E1 cells. Am J Physiol Cell Physiol 290: C1640‐C1650, 2006.
 135. Kheradmand F, Folkesson HG, Shum L, Derynk R, Pytela R, Matthay MA. Transforming growth factor‐alpha enhances alveolar epithelial cell repair in a new in vitro model. Am J Physiol 267: L728‐L738, 1994.
 136. Kim JS, McKinnis VS, Adams K, White SR. Proliferation and repair of guinea pig tracheal epithelium after neuropeptide depletion and injury in vivo. Am J Physiol 273: L1235‐L1241, 1997.
 137. Kojic N, Chung E, Kho AT, Park JA, Huang A, So PT, Tschumperlin DJ. An EGFR autocrine loop encodes a slow‐reacting but dominant mode of mechanotransduction in a polarized epithelium. FASEB J 24: 1604‐1615, 2010.
 138. Kole TP, Tseng Y, Jiang I, Katz JL, Wirtz D. Intracellular mechanics of migrating fibroblasts. Mol Biol Cell 16: 328‐338, 2005.
 139. Kollmannsberger P, Fabry B. High‐force magnetic tweezers with force feedback for biological applications. Rev Sci Instrum 78: 114301, 2007.
 140. Konigshoff M, Balsara N, Pfaff EM, Kramer M, Chrobak I, Seeger W, Eickelberg O. Functional Wnt signaling is increased in idiopathic pulmonary fibrosis. PLoS One 3: e2142, 2008.
 141. Konigshoff M, Eickelberg O. WNT signaling in lung disease: a failure or a regeneration signal? Am J Respir Cell Mol Biol 42: 21‐31, 2010.
 142. Kotecha S. Lung growth for beginners. Paediatr Respir Rev 1: 308‐313, 2000.
 143. Krishnan R, Park CY, Lin YC, Mead J, Jaspers RT, Trepat X, Lenormand G, Tambe D, Smolensky AV, Knoll AH, Butler JP, Fredberg JJ. Reinforcement versus fluidization in cytoskeletal mechanoresponsiveness. Plos One 4: e5486, 2009.
 144. Laifook SJ. Lung parenchyma described as a prestressed compressible material. J Biomech 10: 357‐365, 1977.
 145. Lam AP, Dean DA. Cyclic stretch‐induced nuclear localization of transcription factors results in increased nuclear targeting of plasmids in alveolar epithelial cells. J Gene Med 10: 668‐678, 2008.
 146. Langston C, Sachdeva P, Cowan MJ, Haines J, Crystal RG, Thurlbeck WM. Alveolar multiplication in the contralateral lung after unilateral pneumonectomy in the rabbit. Am Rev Respir Dis 115: 7‐13, 1977.
 147. Lau A, Hoffman B, Davies A, Crocker J, Lubensky T. Microrheology, stress fluctuations, and active behavior of living cells. Phys Rev Lett 91: 198101, 2003.
 148. Lauffenburger DA, Horwitz AF. Cell migration: A physically integrated molecular process. Cell 84: 359‐369, 1996.
 149. Laurent GJ, McAnulty RJ, Hill M, Chambers R. Escape from the matrix: Multiple mechanisms for fibroblast activation in pulmonary fibrosis. Proc Am Thorac Soc 5: 311‐315, 2008.
 150. Laurent VM, Henon S, Planus E, Fodil R, Balland M, Isabey D, Gallet F. Assessment of mechanical properties of adherent living cells by bead micromanipulation: Comparison of magnetic twisting cytometry vs optical tweezers. J Biomech Eng 124: 408‐421, 2002.
 151. Leong WS, Tay CY, Yu H, Li A, Wu SC, Duc DH, Lim CT, Tan LP. Thickness sensing of hMSCs on collagen gel directs stem cell fate. Biochem Biophys Res Commun 401: 287‐292, 2010.
 152. Li QS, Lee GYH, Ong CN, Lim CT. AFM indentation study of breast cancer cells. Biochem Biophys Res Commun 374: 609‐613, 2008.
 153. Li Z, Dranoff JA, Chan EP, Uemura M, Sevigny J, Wells RG. Transforming growth factor‐beta and substrate stiffness regulate portal fibroblast activation in culture. Hepatology 46: 1246‐1256, 2007.
 154. Lionetti V, Recchia FA, Ranieri VM. Overview of ventilator‐induced lung injury mechanisms. Curr Opin Crit Care 11: 82‐86, 2005.
 155. Liu F, Mih JD, Shea BS, Kho AT, Sharif AS, Tager AM, Tschumperlin DJ. Feedback amplification of fibrosis through matrix stiffening and COX‐2 suppression. J Cell Biol 190: 693‐706, 2010.
 156. Macklem PT, Macklem DM, Detroyer A. A model of inspiratory muscle mechanics. J Appl Physiol 55: 547‐557, 1983.
 157. Mahaffy RE, Park S, Gerde E, Kas J, Shih CK. Quantitative analysis of the viscoelastic properties of thin regions of fibroblasts using atomic force microscopy. Biophys J 86: 1777‐1793, 2004.
 158. Maksym GN, Bates JHT. A distributed nonlinear model of lung tissue elasticity. J Appl Physiol 82: 32‐41, 1997.
 159. Maksym GN, Fabry B, Butler JP, Navajas D, Tschumperlin DJ, Laporte JD, Fredberg JJ. Mechanical properties of cultured human airway smooth muscle cells from 0.05 to 0.4 Hz. J Appl Physiol 89: 1619‐1632, 2000.
 160. Maskarinec SA, Franck C, Tirrell DA, Ravichandran G. Quantifying cellular traction forces in three dimensions. P Natl Acad Sci U S A 106: 22108‐22113, 2009.
 161. Mason TG, Weitz DA. Optical measurements of frequency‐dependent linear viscoelastic moduli of complex fluids. Phys Rev Lett 74: 1250‐1253, 1995.
 162. Matheson LA, Jack Fairbank N, Maksym GN, Paul Santerre J, Labow RS. Characterization of the Flexcell(TM) Uniflex(TM) cyclic strain culture system with U937 macrophage‐like cells. Biomaterials 27: 226‐233, 2006.
 163. Matthay MA, Zimmerman GA. Acute lung injury and the acute respiratory distress syndrome: Four decades of inquiry into pathogenesis and rational management. Am J Respir Cell Mol Biol 33: 319‐327, 2005.
 164. Matthews BD, Overby DR, Alenghat FJ, Karavitis J, Numaguchi Y, Allen PG, Ingber DE. Mechanical properties of individual focal adhesions probed with a magnetic microneedle. Biochem Biophys Res Commun 313: 758‐764, 2004.
 165. McAdams RM, Mustafa SB, Shenberger JS, Dixon PS, Henson BM, DiGeronimo RJ. Cyclic stretch attenuates effects of hyperoxia on cell proliferation and viability in human alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 291: L166‐L174, 2006.
 166. McAnulty RJ, Laurent GJ. Collagen‐synthesis and degradation in vivo. Evidence for rapid rates of collagen turnover with extensive degradation of newly synthesized collagen in tissues of the adult‐rat. Coll Relat Res 7: 93‐104, 1987.
 167. McCann UG, 2nd, Schiller HJ, Carney DE, Gatto LA, Steinberg JM, Nieman GF. Visual validation of the mechanical stabilizing effects of positive end‐expiratory pressure at the alveolar level. J Surg Res 99: 335‐342, 2001.
 168. Mead J, Takishim T, Leith D. Stress distribution in lungs: A model of pulmonary elasticity. J Appl Physiol 28: 596‐608, 1970.
 169. Mendez JL, Hubmayr RD. New insights into the pathology of acute respiratory failure. Curr Opin Crit Care 11: 29‐36, 2005.
 170. Mercer RR, Crapo JD. Spatial distribution of collagen and elastin fibers in the lungs. J Appl Physiol 69: 756‐765, 1990.
 171. Meurs H, Gosens R, Zaagsma J. Airway hyperresponsiveness in asthma: Lessons from in vitro model systems and animal models. Eur Respir J 32: 487‐502, 2008.
 172. Mijailovich SM, Kojic M, Zivkovic M, Fabry B, Fredberg JJ. A finite element model of cell deformation during magnetic bead twisting. J Appl Physiol 93: 1429‐1436, 2002.
 173. Mitchison TJ, Swann MM. The mechanical properties of the cell surface: I. The cell elastimeter. J Exp Biol 31: 443‐460, 1954.
 174. Moessinger AC, Harding R, Adamson TM, Singh M, Kiu GT. Role of lung fluid volume in growth and maturation of the fetal sheep lung. J Clin Invest 86: 1270‐1277, 1990.
 175. Moraes C, Chen JH, Sun Y, Simmons CA. Microfabricated arrays for high‐throughput screening of cellular response to cyclic substrate deformation. Lab on a Chip 10: 227‐234, 2010.
 176. Moretti M, Prina‐Mello A, Reid AJ, Barron V, Prendergast PJ. Endothelial cell alignment on cyclically‐stretched silicone surfaces. J Mater Sci Mater Med 15: 1159‐1164, 2004.
 177. Muscedere JG, Mullen JB, Gan K, Slutsky AS. Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 149: 1327‐1334, 1994.
 178. Nardo L, Maritz G, Harding R, Hooper SB. Changes in lung structure and cellular division induced by tracheal obstruction in fetal sheep. Exp Lung Res 26: 105‐119, 2000.
 179. Navajas D, Maksym GN, Bates JHT. Dynamic viscoelastic nonlinearity of lung parenchymal tissue. J Appl Physiol 79: 348‐356, 1995.
 180. Needham D, Hochmuth RM. Rapid flow of passive neutrophils into a 4 Mu‐M pipette and measurement of cytoplasmic viscosity. J Biomech Eng 112: 269‐276, 1990.
 181. Neuman KC, Chadd EH, Liou GF, Bergman K, Block SM. Characterization of photodamage to Escherichia coli in optical traps. Biophys J 77: 2856‐2863, 1999.
 182. Nicholas TE, Barr HA. Control of release of surfactant phospholipids in the isolated perfused rat lung. J Appl Physiol 51: 90‐98, 1981.
 183. Ning QM, Wang XR. Response of alveolar type II epithelial cells to mechanical stretch and lipopolysaccharide. Respiration 74: 579‐585, 2007.
 184. Oeckler RA, Hubmayr RD. Alveolar microstrain and the dark side of the lung. Crit Care 11: 177, 2007.
 185. Oeckler RA, Hubmayr RD. Cell wounding and repair in ventilator injured lungs. Respir Physiol Neurobiol 163: 44‐53, 2008.
 186. Oeckler RA, Lee WY, Park MG, Kofler O, Rasmussen DL, Lee HB, Belete H, Walters BJ, Stroetz RW, Hubmayr RD. Determinants of plasma membrane wounding by deforming stress. Am J Physiol Lung Cell Mol Physiol 299: L826‐L833, 2010.
 187. Oldmixon EH, Hoppin FG, Jr.. Alveolar septal folding and lung inflation history. J Appl Physiol 71: 2369‐2379, 1991.
 188. Panettieri RA, Jr., Kotlikoff MI, Gerthoffer WT, Hershenson MB, Woodruff PG, Hall IP, Banks‐Schlegel S. Airway smooth muscle in bronchial tone, inflammation, and remodeling: Basic knowledge to clinical relevance. Am J Respir Crit Care Med 177: 248‐252, 2008.
 189. Papaiahgari S, Yerrapureddy A, Hassoun PM, Garcia JG, Birukov KG, Reddy SP. EGFR‐activated signaling and actin remodeling regulate cyclic stretch‐induced NRF2‐ARE activation. Am J Respir Cell Mol Biol 36: 304‐312, 2007.
 190. Papakonstantinou E, Karakiulakis G. The ‘sweet’ and ‘bitter’ involvement of glycosaminoglycans in lung diseases: Pharmacotherapeutic relevance. Br J Pharmacol 157: 1111‐1127, 2009.
 191. Park JA, Drazen JM, Tschumperlin DJ. The chitinase‐like protein YKL‐40 is secreted by airway epithelial cells at base line and in response to compressive mechanical stress. J Biol Chem 285: 29817‐29825, 2010.
 192. Park JA, Tschumperlin DJ. Chronic intermittent mechanical stress increases MUC5AC protein expression. Am J Respir Cell Mol Biol 41: 459‐466, 2009.
 193. Patel AS, Reigada D, Mitchell CH, Bates SR, Margulies SS, Koval M. Paracrine stimulation of surfactant secretion by extracellular ATP in response to mechanical deformation. Am J Physiol Lung Cell Mol Physiol 289: L489‐L496, 2005.
 194. Patel H, Kwon S. Interplay between cytokine‐induced and cyclic equibiaxial deformation‐induced nitric oxide production and metalloproteases expression in human alveolar epithelial cells. Cell Mol Bioeng 4: 615‐624, 2009.
 195. Pelosi P, Rocco PR. Effects of mechanical ventilation on the extracellular matrix. Intensive Care Med 34: 631‐639, 2008.
 196. Perlman CE, Bhattacharya J. Alveolar expansion imaged by optical sectioning microscopy. J Appl Physiol 103: 1037‐1044, 2007.
 197. Perlman CE, Lederer DJ, Bhattacharya J. The micromechanics of alveolar edema. Am J Respir Cell Mol Biol 44: 34‐39, 2010.
 198. Pfister BJ, Weihs TP, Betenbaugh M, Bao G. An in vitro uniaxial stretch model for axonal injury. Ann Biomed Eng 31: 589‐598, 2003.
 199. Pinart M, Serrano‐Mollar A, Llatjos R, Rocco PR, Romero PV. Single and repeated bleomycin intratracheal instillations lead to different biomechanical changes in lung tissue. Respir Physiol Neurobiol 166: 41‐46, 2009.
 200. Pingleton SK. Complications of acute respiratory failure. Am Rev Respir Dis 137: 1463‐1493, 1988.
 201. Pinhu L, Whitehead T, Evans T, Griffiths M. Ventilator‐associated lung injury. Lancet 361: 332‐340, 2003.
 202. Puchelle E, Zahm JM, Tournier JM, Coraux C. Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease. Proc Am Thorac Soc 3: 726‐733, 2006.
 203. Pugin J, Dunn‐Siegrist I, Dufour J, Tissières P, Charles PE, Comte R. Cyclic stretch of human lung cells induces an acidification and promotes bacterial growth. Am J Respir Cell Mol Biol 38: 362‐370, 2008.
 204. Puig‐de‐Morales M, Grabulosa M, Alcaraz J, Mullol J, Maksym GN, Fredberg JJ, Navajas D. Measurement of cell microrheology by magnetic twisting cytometry with frequency domain demodulation. J Appl Physiol 91: 1152‐1159, 2001.
 205. Rana OR, Zobel C, Saygili E, Brixius K, Gramley F, Schimpf T, Mischke K, Frechen D, Knackstedt C, Schwinger RHG, Schauerte P, Saygili E. A simple device to apply equibiaxial strain to cells cultured on flexible membranes. Am J Physiol Heart Circ Physiol 294: H532‐H540, 2008.
 206. Rannels DE. Role of physical forces in compensatory growth of the lung. Am J Physiol 257: L179‐L189, 1989.
 207. Rannels DE, Stockstill B, Mercer RR, Crapo JD. Cellular changes in the lungs of adrenalectomized rats following left pneumonectomy. Am J Respir Cell Mol Biol 5: 351‐362, 1991.
 208. Rannels DE, White DM, Watkins CA. Rapidity of compensatory lung growth following pneumonectomy in adult rats. J Appl Physiol 46: 326‐333, 1979.
 209. Raucher D, Sheetz MP. Cell spreading and lamellipodial extension rate is regulated by membrane tension. J Cell Biol 148: 127‐136, 2000.
 210. Ren Y, Zhan Q, Hu Q, Sun B, Yang C, Wang C. Static stretch induces active morphological remodeling and functional impairment of alveolar epithelial cells. Respiration 78: 301‐311, 2009.
 211. Ricard JD, Dreyfuss D, Saumon G. Ventilator‐induced lung injury. Eur Respir J Suppl 42: 2s‐9s, 2003.
 212. Rico F, Roca‐Cusachs P, Gavara N, Farre R, Rotger M, Navajas D. Probing mechanical properties of living cells by atomic force microscopy with blunted pyramidal cantilever tips. Phys Rev E 72: 021914, 2005.
 213. Rico F, Roca‐Cusachs P, Sunyer R, Farre R, Navajas D. Cell dynamic adhesion and elastic properties probed with cylindrical atomic force microscopy cantilever tips. J Mol Recognit 20: 459‐466, 2007.
 214. Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR. Cell migration: Integrating signals from front to back. Science 302: 1704‐1709, 2003.
 215. Roca‐Cusachs P, Almendros I, Sunyer R, Gavara N, Farre R, Navajas D. Rheology of passive and adhesion‐activated neutrophils probed by atomic force microscopy. Biophys J 91: 3508‐3518, 2006.
 216. Sanchez‐Esteban J, Cicchiello LA, Wang Y, Tsai SW, Williams LK, Torday JS, Rubin LP. Mechanical stretch promotes alveolar epithelial type II cell differentiation. J Appl Physiol 91: 589‐595, 2001.
 217. Sasaki N, Odajima S. Stress‐strain curve and young's modulus of a collagen molecule as determined by the X‐ray diffraction technique. J Biomech 29: 655‐658, 1996.
 218. Savla U, Olson LE, Waters CM. Mathematical modeling of airway epithelial wound closure during cyclic mechanical strain. J Appl Physiol 96: 566‐574, 2004.
 219. Savla U, Waters CM. Mechanical strain inhibits repair of airway epithelium in vitro. Am J Physiol 274: L883‐L892, 1998.
 220. Schaffer JL, Rizen M, Litalien GJ, Benbrahim A, Megerman J, Gerstenfeld LC, Gray ML. Device for the application of a dynamic biaxially uniform and isotropic strain to a flexible cell‐culture membrane. J Orth Res 12: 709‐719, 1994.
 221. Schiller HJ, Steinberg J, Halter J, McCann U, DaSilva M, Gatto LA, Carney D, Nieman G. Alveolar inflation during generation of a quasi‐static pressure/volume curve in the acutely injured lung. Crit Care Med 31: 1126‐1133, 2003.
 222. Scuor N, Gallina P, Panchawagh HV, Mahajan RL, Sbaizero O, Sergo V. Design of a novel MEMS platform for the biaxial stimulation of living cells. Biomed Microdevices 8: 239‐246, 2006.
 223. Selby JC, Shannon MA. Mechanical response of a living human epidermal keratinocyte sheet as measured in a composite diaphragm inflation experiment. Biorheology 44: 319‐348, 2007.
 224. Shannon JM, Jennings SD, Nielsen LD. Modulation of alveolar type II cell differentiated function in vitro. Am J Physiol 262: L427‐L436, 1992.
 225. Shen X, Gunst SJ, Tepper RS. Effect of tidal volume and frequency on airway responsiveness in mechanically ventilated rabbits. J Appl Physiol 83: 1202‐1208, 1997.
 226. Silbert O, Wang Y, Maciejewski BS, Lee HS, Shaw SK, Sanchez‐Esteban J. Roles of RhoA and Rac1 on actin remodeling and cell alignment and differentiation in fetal type II epithelial cells exposed to cyclic mechanical stretch. Exp Lung Res 34: 663‐680, 2008.
 227. Silver FH, Freeman JW, Seehra GP. Collagen self‐assembly and the development of tendon mechanical properties. J Biomech 36: 1529‐1553, 2003.
 228. Smith BA, Tolloczko B, Martin JG, Grutter P. Probing the viscoelastic behavior of cultured airway smooth muscle cells with atomic force microscopy: Stiffening induced by contractile agonist. Biophys J 88: 2994‐3007, 2005.
 229. Smith BJ, Yamaguchi E, Gaver DP, 3rd. A translating stage system for micro‐PIV measurements surrounding the tip of a migrating semi‐infinite bubble. Meas Sci Technol 21: 1‐13, 2010.
 230. Sotoudeh M, Jalali S, Usami S, Shyy JYJ, Chien S. A strain device imposing dynamic and uniform equi‐biaxial strain to cultured cells. Ann Biomed Eng 26: 181‐189, 1998.
 231. Stamenovic D. Micromechanical foundations of pulmonary elasticity. Physiol Rev 70: 1117‐1134, 1990.
 232. Steinberg J, Schiller HJ, Halter JM, Gatto LA, Dasilva M, Amato M, McCann UG, Nieman GF. Tidal volume increases do not affect alveolar mechanics in normal lung but cause alveolar overdistension and exacerbate alveolar instability after surfactant deactivation. Crit Care Med 30: 2675‐2683, 2002.
 233. Stripp BR, Reynolds SD. Maintenance and repair of the bronchiolar epithelium. Proc Am Thorac Soc 5: 328‐333, 2008.
 234. Stroetz RW, Vlahakis NE, Walters BJ, Schroeder MA, Hubmayr RD. Validation of a new live cell strain system: characterization of plasma membrane stress failure. J Appl Physiol 90: 2361‐2370, 2001.
 235. Suki B, Bates JHT. Extracellular matrix mechanics in lung parenchymal diseases. Respir Physiol Neurobiol 163: 33‐43, 2008.
 236. Suki B, Lutchen KR, Ingenito EP. On the progressive nature of emphysema: Roles of proteases, inflammation, and mechanical forces. Am J Respir Crit Care Med 168: 516‐521, 2003.
 237. Suki B, Majumdar A, Nugent MA, Bates JH. In silico modeling of interstitial lung mechanics: Implications for disease development and repair. Drug Discov Today Dis Models 4: 139‐145, 2007.
 238. Sunyer R, Trepat X, Fredberg JJ, Farre R, Navajas D. The temperature dependence of cell mechanics measured by atomic force microscopy. Phys Biol 6: 025009‐025010, 2009.
 239. Swindle EJ, Collins JE, Davies DE. Breakdown in epithelial barrier function in patients with asthma: Identification of novel therapeutic approaches. J Allergy Clin Immunol 124: 23‐34, 2009.
 240. Tan JL, Tien J, Pirone DM, Gray DS, Bhadriraju K, Chen CS. Cells lying on a bed of microneedles: An approach to isolate mechanical force. Proc Natl Acad Sci U S A 100: 1484‐1489, 2003.
 241. Tan W, Scott D, Belchenko D, Qi HJ, Xiao L. Development and evaluation of microdevices for studying anisotropic biaxial cyclic stretch on cells. Biomed Microdevices 10: 869‐882, 2008.
 242. Tang X, Kuhlenschmidt TB, Zhou J, Bell P, Wang F, Kuhlenschmidt MS, Saif TA. Mechanical force affects expression of an in vitro metastasis‐like phenotype in HCT‐8 cells. Biophys J 99: 2460‐2469, 2010.
 243. Taskar V, John J, Evander E, Robertson B, Jonson B. Surfactant dysfunction makes lungs vulnerable to repetitive collapse and reexpansion. Am J Respir Crit Care Med 155: 313‐320, 1997.
 244. Tavana H, Kuo CH, Lee QY, Mosadegh B, Huh D, Christensen PJ, Grotberg JB, Takayama S. Dynamics of liquid plugs of buffer and surfactant solutions in a micro‐engineered pulmonary airway model. Langmuir 26: 3744‐3752, 2010.
 245. Tepper RS, Shen X, Bakan E, Gunst SJ. Maximal airway response in mature and immature rabbits during tidal ventilation. J Appl Physiol 79: 1190‐1198, 1995.
 246. Thet LA, Law DJ. Changes in cell number and lung morphology during early postpneumonectomy lung growth. J Appl Physiol 56: 975‐978, 1984.
 247. Thoumine O, Ott A. Time scale dependent viscoelastic and contractile regimes in fibroblasts probed by microplate manipulation. J Cell Sci 110: 2109‐2116, 1997.
 248. Toshima M, Ohtani Y, Ohtani O. Three‐dimensional architecture of elastin and collagen fiber networks in the human and rat lung. Arch Histol Cytol 67: 31‐40, 2004.
 249. Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS. Injurious ventilatory strategies increase cytokines and c‐fos m‐RNA expression in an isolated rat lung model. J Clin Invest 99: 944‐952, 1997.
 250. Tremblay LN, Miatto D, Hamid Q, Govindarajan A, Slutsky AS. Injurious ventilation induces widespread pulmonary epithelial expression of tumor necrosis factor‐alpha and interleukin‐6 messenger RNA. Crit Care Med 30: 1693‐1700, 2002.
 251. Tremblay LN, Slutsky AS. Ventilator‐induced injury: From barotrauma to biotrauma. Proc Assoc Am Physicians 110: 482‐488, 1998.
 252. Tremblay LN, Slutsky AS. Ventilator‐induced lung injury: From the bench to the bedside. Intensive Care Med 32: 24‐33, 2006.
 253. Trepat X, Deng LH, An SS, Navajas D, Tschumperlin DJ, Gerthoffer WT, Butler JP, Fredberg JJ. Universal physical responses to stretch in the living cell. Nature 447: 592‐595, 2007.
 254. Trepat X, Grabulosa M, Buscemi L, Rico F, Fabry B, Fredberg JJ, Farre R. Oscillatory magnetic tweezers based on ferromagnetic beads and simple coaxial coils. Rev Sci Instrum 74: 4012‐4020, 2003.
 255. Trepat X, Grabulosa M, Puig F, Maksym GN, Navajas D, Farre R. Viscoelasticity of human alveolar epithelial cells subjected to stretch. Am J Physiol Lung Cell Mol Physiol 287: L1025‐L1034, 2004.
 256. Trepat X, Puig F, Gavara N, Fredberg JJ, Farre R, Navajas D. Effect of stretch on structural integrity and micromechanics of human alveolar epithelial cell monolayers exposed to thrombin. Am J Physiol Lung Cell Mol Physiol 290: L1104‐L1110, 2006.
 257. Tschumperlin DJ, Dai G, Maly IV, Kikuchi T, Laiho LH, McVittie AK, Haley KJ, Lilly CM, So PT, Lauffenburger DA, Kamm RD, Drazen JM. Mechanotransduction through growth‐factor shedding into the extracellular space. Nature 429: 83‐86, 2004.
 258. Tschumperlin DJ, Drazen JM. Chronic effects of mechanical force on airways. Annu Rev Physiol 68: 563‐583, 2006.
 259. Tschumperlin DJ, Margulies SS. Equibiaxial deformation‐induced injury of alveolar epithelial cells in vitro. Am J Physiol 275: L1173‐L1183, 1998.
 260. Tschumperlin DJ, Margulies SS. Alveolar epithelial surface area‐volume relationship in isolated rat lungs. J Appl Physiol 86: 2026‐2033, 1999.
 261. Tschumperlin DJ, Oswari J, Margulies AS. Deformation‐induced injury of alveolar epithelial cells. Effect of frequency, duration, and amplitude. Am J Respir Crit Care Med 162: 357‐362, 2000.
 262. Tschumperlin DJ, Shively JD, Kikuchi T, Drazen JM. Mechanical stress triggers selective release of fibrotic mediators from bronchial epithelium. Am J Respir Cell Mol Biol 28: 142‐149, 2003.
 263. Van Citters KM, Hoffman BD, Massiera G, Crocker JC. The role of F‐actin and myosin in epithelial cell rheology. Biophys J 91: 3946‐3956, 2006.
 264. Venkatesan N, Ebihara T, Roughley PJ, Ludwig MS. Alterations in large and small proteoglycans in bleomycin‐induced pulmonary fibrosis in rats. Am J Respir Crit Care Med 161: 2066‐2073, 2000.
 265. Vlahakis NE, Hubmayr RD. Invited review: Plasma membrane stress failure in alveolar epithelial cells. J Appl Physiol 89: 2490‐2496; discussion 2497, 2000.
 266. Vlahakis NE, Hubmayr RD. Cellular stress failure in ventilator‐injured lungs. Am J Respir Crit Care Med 171: 1328‐1342, 2005.
 267. Vlahakis NE, Schroeder MA, Limper AH, Hubmayr RD. Stretch induces cytokine release by alveolar epithelial cells in vitro. Am J Physiol 277: L167‐L173, 1999.
 268. Vlahakis NE, Schroeder MA, Pagano RE, Hubmayr RD. Deformation‐induced lipid trafficking in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 280: L938‐L946, 2001.
 269. Vlahakis NE, Schroeder MA, Pagano RE, Hubmayr RD. Role of deformation‐induced lipid trafficking in the prevention of plasma membrane stress failure. Am J Respir Crit Care Med 166: 1282‐1289, 2002.
 270. Wagh AA, Roan E, Chapman KE, Desai LP, Rendon DA, Eckstein EC, Waters CM. Localized elasticity measured in epithelial cells migrating at a wound edge using atomic force microscopy. Am J Physiol Lung Cell Mol Physiol 295: L54‐L60, 2008.
 271. Wall ME, Weinhold PS, Siu T, Brown TD, Banes AJ. Comparison of cellular strain with applied substrate strain in vitro. J Biomech 40: 173‐181, 2007.
 272. Wang JHC, Yang GG, Li ZZ. Controlling cell responses to cyclic mechanical stretching. Ann Biomed Eng 33: 337‐342, 2005.
 273. Wang N, Butler JP, Ingber DE. Mechanotransduction across the cell‐surface and through the cytoskeleton. Science 260: 1124‐1127, 1993.
 274. Wang N, Tolic‐Norrelykke IM, Chen JX, Mijailovich SM, Butler JP, Fredberg JJ, Stamenovic D. Cell prestress. I. Stiffness and prestress are closely associated in adherent contractile cells. Am J Physiol Cell Physiol 282: C606‐C616, 2002.
 275. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 342: 1334‐1349, 2000.
 276. Warner DO, Gunst SJ. Limitation of maximal bronchoconstriction in living dogs. Am Rev Respir Dis 145: 553‐560, 1992.
 277. Waters CM, Glucksberg MR, Lautenschlager EP, Lee CW, Van Matre RM, Warp RJ, Savla U, Healy KE, Moran B, Castner DG, Bearinger JP. A system to impose prescribed homogenous strains on cultured cells. J Appl Physiol 91: 1600‐1610, 2001.
 278. Waters CM, Ridge KM, Sunio G, Venetsanou K, Sznajder JI. Mechanical stretching of alveolar epithelial cells increases Na(+)‐K(+)‐ATPase activity. J Appl Physiol 87: 715‐721, 1999.
 279. Waters CM, Savla U. Keratinocyte growth factor accelerates wound closure in airway epithelium during cyclic mechanical strain. J Cell Physiol 181: 424‐432, 1999.
 280. Waugh R, Evans EA. Thermoelasticity of red blood‐cell membrane. Biophys J 26: 115‐131, 1979.
 281. Webb HH, Tierney DF. Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end‐expiratory pressure. Am Rev Respir Dis 110: 556‐565, 1974.
 282. Wei MT, Zaorski A, Yalcin HC, Wang J, Hallow M, Ghadiali SN, Chiou A, Ou‐Yang HD. A comparative study of living cell micromechanical properties by oscillatory optical tweezers. Optics Express 16: 8594‐8603, 2008.
 283. Weibel E. The Pathway for Oxygen. Structure and Function in the Mammalian Respiratory System. Cambridge, UK: Harvard University Press, 1984.
 284. West JB. Invited review: Pulmonary capillary stress failure. J Appl Physiol 89: 2483‐2489; discussion 2497, 2000.
 285. Westergrenthorsson G, Hernnas J, Sarnstrad B, Oldberg A, Heinegard D, Malmstrom A. Altered expression of small proteoglycans, collagen, and transforming growth factor‐beta 1 in developing bleomycin‐induced pulmonary fibrosis in rats. J Clin Invest 92: 632‐637, 1993.
 286. Wigglesworth JS, Desai R. Effect on lung growth of cervical cord section in the rabbit fetus. Early Hum Dev 3: 51‐65, 1979.
 287. Wiggs BR, Hrousis CA, Drazen JM, Kamm RD. On the mechanism of mucosal folding in normal and asthmatic airways. J Appl Physiol 83: 1814‐1821, 1997.
 288. Williams J, Chen J, Belloli D. Strain fields on cell stressing devices employing clamped circular elastic diaphragms as substrates. J Biomech Eng 114: 377‐384, 1992.
 289. Wilson TA, Bachofen H. A model for mechanical structure of the alveolar duct. J Appl Physiol 52: 1064‐1070, 1982.
 290. Winston FK, Macarak EJ, Gorfien SF, Thibault LE. A system to reproduce and quantify the biomechanical environment of the cell. J Appl Physiol 67: 397‐405, 1989.
 291. Wirtz HR, Dobbs LG. Calcium mobilization and exocytosis after one mechanical stretch of lung epithelial cells. Science 250: 1266‐1269, 1990.
 292. Wirtz HR, Dobbs LG. The effects of mechanical forces on lung functions. Respir Physiol 119: 1‐17, 2000.
 293. Wu Q, Shu H, Yao S, Xiang H. Mechanical stretch induces pentraxin 3 release by alveolar epithelial cells in vitro. Med Sci Monit 15: BR135‐B140, 2009.
 294. Wyszogrodski I, Taeusch HW, Jr., Kyei‐Aboagye K, Avery ME. Mechanical regulation of alveolar surfactant in adult cats: the effects of hyperventilation and end‐expiratory pressure in vivo. Chest 67: 15S‐16S, 1975.
 295. Xue Z, Zhang L, Liu Y, Gunst SJ, Tepper RS. Chronic inflation of ferret lungs with CPAP reduces airway smooth muscle contractility in vivo and in vitro. J Appl Physiol 104: 610‐615, 2008.
 296. Xue Z, Zhang L, Ramchandani R, Liu Y, Antony VB, Gunst SJ, Tepper RS. Respiratory system responsiveness in rabbits in vivo is reduced by prolonged continuous positive airway pressure. J Appl Physiol 99: 677‐682, 2005.
 297. Yalcin HC, Hallow KM, Wang J, Wei MT, Ou‐Yang HD, Ghadiali SN. Influence of cytoskeletal structure and mechanics on epithelial cell injury during cyclic airway reopening. Am J Physiol Lung Cell Mol Physiol 297: L881‐L891, 2009.
 298. Yalcin HC, Perry SF, Ghadiali SN. Influence of airway diameter and cell confluence on epithelial cell injury in an in vitro model of airway reopening. J Appl Physiol 103: 1796‐1807, 2007.
 299. Yamada S, Wirtz D, Kuo SC. Mechanics of living cells measured by laser tracking microrheology. Biophys J 78: 1736‐1747, 2000.
 300. Yerrapureddy A, Tobias J, Margulies SS. Cyclic stretch magnitude and duration affect rat alveolar epithelial gene expression. Cell Physiol Biochem 25: 113‐122, 2010.
 301. Yeung A, Evans E. Cortical shell‐liquid core model for passive flow of liquid‐like spherical cells into micropipets. Biophys J 56: 139‐149, 1989.
 302. Yuan H, Ingenito EP, Suki B. Dynamic properties of lung parenchyma: Mechanical contributions of fiber network and interstitial cells. J ApplPhysiol 83: 1420‐1431, 1997.

Related Articles:

Gas Exchange in Disease: Asthma, Chronic Obstructive Pulmonary Disease, Cystic Fibrosis, and Interstitial Lung Disease
Development and Growth of the Human Lung
Distribution of Stresses Within the Lung
Lung Mechanics in Disease
Lung Recoil: Elastic and Rheological Properties
Mechanotransduction
Micromechanics of the Lung
Respiratory Mechanics During Anesthesia and Mechanical Ventilation
Solid Mechanics
Stress Transmission within the Cell
Ventilation‐Induced Lung Injury
Fluid Flux and Clearance in Acute Lung Injury
Gaseous Therapeutics in Acute Lung Injury

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Christopher M. Waters, Esra Roan, Daniel Navajas. Mechanobiology in Lung Epithelial Cells: Measurements, Perturbations, and Responses. Compr Physiol 2012, 2: 1-29. doi: 10.1002/cphy.c100090