Traction in smooth muscle cells varies with cell spreading.

Changes in cell shape regulate cell growth, differentiation, and apoptosis. It has been suggested that the regulation of cell function by the cell shape is a result of the tension in the cytoskeleton and the distortion of the cell. Here we explore the association between cell-generated mechanical forces and the cell morphology. We hypothesized that the cell contractile force is associated with the degree of cell spreading, in particular with the cell length. We measured traction fields of single human airway smooth muscle cells plated on a polyacrylamide gel, in which fluorescent microbeads were embedded to serve as markers of gel deformation. The traction exerted by the cells at the cell-substrate interface was determined from the measured deformation of the gel. The traction was measured before and after treatment with the contractile agonist histamine, or the relaxing agonist isoproterenol. The relative increase in traction induced by histamine was negatively correlated with the baseline traction. On the contrary, the relative decrease in traction due to isoproterenol was independent of the baseline traction, but it was associated with cell shape: traction decreased more in elongated than in round cells. Maximum cell width, mean cell width, and projected area of the cell were the parameters most tightly coupled to both baseline and histamine-induced traction in this study. Wide and well-spread cells exerted larger traction than slim cells. These results suggest that cell contractility is controlled by cell spreading.

[1]  R G Dennis,et al.  Microtubule assembly is regulated by externally applied strain in cultured smooth muscle cells. , 1998, Journal of cell science.

[2]  D E Ingber,et al.  Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. , 1994, Biophysical journal.

[3]  D. Ingber,et al.  Extracellular matrix and pulmonary hypertension : control of vascular smooth muscle cell contractility , 1997 .

[4]  Ning Wang,et al.  Spatial and temporal traction response in human airway smooth muscle cells. , 2002, American journal of physiology. Cell physiology.

[5]  Daniel I. C. Wang,et al.  Engineering cell shape and function. , 1994, Science.

[6]  C. S. Chen,et al.  Geometric control of cell life and death. , 1997, Science.

[7]  Ben Fabry,et al.  Traction fields, moments, and strain energy that cells exert on their surroundings. , 2002, American journal of physiology. Cell physiology.

[8]  Jean Lai,et al.  Stiffness changes in cultured airway smooth muscle cells. , 2002, American journal of physiology. Cell physiology.

[9]  C. S. Chen,et al.  Control of cyclin D1, p27(Kip1), and cell cycle progression in human capillary endothelial cells by cell shape and cytoskeletal tension. , 1998, Molecular biology of the cell.

[10]  D. Stamenović,et al.  Cell prestress. I. Stiffness and prestress are closely associated in adherent contractile cells. , 2002, American journal of physiology. Cell physiology.

[11]  W. Petroll,et al.  Direct correlation of collagen matrix deformation with focal adhesion dynamics in living corneal fibroblasts , 2003, Journal of Cell Science.

[12]  D. Ingber,et al.  Apoptosis of syncytia induced by the HIV-1-envelope glycoprotein complex: influence of cell shape and size. , 2000, Experimental cell research.

[13]  W. H. Reid,et al.  The Theory of Elasticity , 1960 .

[14]  Ning Wang,et al.  Is cytoskeletal tension a major determinant of cell deformability in adherent endothelial cells? , 1998, American journal of physiology. Cell physiology.

[15]  V Berezin,et al.  A simple procedure for morphometric analysis of processes and growth cones of neurons in culture using parameters derived from the contour and convex hull of the object 1 More information about the software can be obtained from the authors. 1 , 1998, Journal of Neuroscience Methods.

[16]  S. Timoshenko,et al.  Theory of elasticity , 1975 .

[17]  J J Fredberg,et al.  Selected contribution: time course and heterogeneity of contractile responses in cultured human airway smooth muscle cells. , 2001, Journal of applied physiology.

[18]  Donald E Ingber,et al.  Micropatterning tractional forces in living cells. , 2002, Cell motility and the cytoskeleton.

[19]  D E Ingber,et al.  Fibronectin controls capillary endothelial cell growth by modulating cell shape. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[20]  C. S. Chen,et al.  Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Christopher S. Chen,et al.  Cells lying on a bed of microneedles: An approach to isolate mechanical force , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Molloy,et al.  Contractility of single human dermal myofibroblasts and fibroblasts. , 2002, Cell motility and the cytoskeleton.

[23]  C. Feldherr,et al.  The permeability of the nuclear envelope in dividing and nondividing cell cultures , 1990, The Journal of cell biology.

[24]  J J Fredberg,et al.  Pharmacological activation changes stiffness of cultured human airway smooth muscle cells. , 1996, The American journal of physiology.

[25]  M. Dembo,et al.  Stresses at the cell-to-substrate interface during locomotion of fibroblasts. , 1999, Biophysical journal.

[26]  M Nathan,et al.  Friction in airway smooth muscle: mechanism, latch, and implications in asthma. , 1996, Journal of applied physiology.

[27]  D. Ingber,et al.  Regulation of cytoskeletal mechanics and cell growth by myosin light chain phosphorylation. , 1998, The American journal of physiology.

[28]  Kevin E. Healy,et al.  Engineering gene expression and protein synthesis by modulation of nuclear shape , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[29]  G. Whitesides,et al.  Control of endothelial focal adhesions by cell shape , 1999, Proceedings of the First Joint BMES/EMBS Conference. 1999 IEEE Engineering in Medicine and Biology 21st Annual Conference and the 1999 Annual Fall Meeting of the Biomedical Engineering Society (Cat. N.

[30]  S. Gunst,et al.  The contractile apparatus and mechanical properties of airway smooth muscle. , 2000, The European respiratory journal.

[31]  N. Balaban,et al.  Force and focal adhesion assembly , 2001 .

[32]  Y. Wang,et al.  High resolution detection of mechanical forces exerted by locomoting fibroblasts on the substrate. , 1999, Molecular biology of the cell.

[33]  L. Addadi,et al.  Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates , 2001, Nature Cell Biology.

[34]  D. Ingber,et al.  Altering the cellular mechanical force balance results in integrated changes in cell, cytoskeletal and nuclear shape. , 1992, Journal of cell science.

[35]  I M Gelfand,et al.  Mechanisms of polarization of the shape of fibroblasts and epitheliocytes: Separation of the roles of microtubules and Rho-dependent actin–myosin contractility , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[36]  T. Desai,et al.  Inhibition of fibroblast proliferation in cardiac myocyte cultures by surface microtopography. , 2003, American journal of physiology. Cell physiology.