Is the mechanical activity of epithelial cells controlled by deformations or forces?

The traction forces developed by cells depend strongly on the substrate rigidity. In this letter, we characterize quantitatively this effect on MDCK epithelial cells by using a microfabricated force sensor consisting in a high-density array of soft pillars whose stiffness can be tailored by changing their height and radius to obtain a rigidity range from 2 nN/microm up to 130 nN/microm. We find that the forces exerted by the cells are proportional to the spring constant of the pillars meaning that, on average, the cells deform the pillars by the same amount whatever their rigidity. The relevant parameter may thus be a deformation rather than a force. These dynamic observations are correlated with the reinforcement of focal adhesions that increases with the substrate rigidity.

[1]  M. Sheetz,et al.  A micromachined device provides a new bend on fibroblast traction forces. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

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

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

[4]  Lev Davidovich Landau,et al.  Théorie de l"élasticité , 1990 .

[5]  M. Dembo,et al.  Cell movement is guided by the rigidity of the substrate. , 2000, Biophysical journal.

[6]  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.

[7]  Daniel Choquet,et al.  Extracellular Matrix Rigidity Causes Strengthening of Integrin–Cytoskeleton Linkages , 1997, Cell.

[8]  Y. Wang,et al.  Cell locomotion and focal adhesions are regulated by substrate flexibility. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[9]  P. Janmey,et al.  Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. , 2005, Cell motility and the cytoskeleton.

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

[11]  R. Austin,et al.  Force mapping in epithelial cell migration. , 2005, Proceedings of the National Academy of Sciences of the United States of America.