A bio-mechanical model for coupling cell contractility with focal adhesion formation

Vikram S. Deshpande*, Milan Mrksich, Robert M. McMeeking, Anthony G. Evans

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Focal adhesions (FAs) are large, multi-protein complexes that provide a mechanical link between the cytoskeletal contractile machinery and the extracellular matrix. They exhibit mechanosensitive properties; they self-assemble upon application of pulling forces and dissociate when these forces are decreased. We rationalize this mechano-sensitivity from thermodynamic considerations and develop a continuum framework in which the cytoskeletal contractile forces generated by stress fibers drive the assembly of the FA multi-protein complexes. The FA model has three essential features: (i) the low and high affinity integrins co-exist in thermodynamic equilibrium, (ii) the low affinity integrins within the plasma membrane are mobile, and (iii) the contractile forces generated by the stress fibers are in mechanical equilibrium and change the free energies of the integrins. A general two-dimensional framework is presented and the essential features of the model illustrated using one-dimensional examples. Consistent with observations, the coupled stress fiber and FA model predict that (a) the FAs concentrate around the periphery of the cell; (b) the fraction of the cell covered by FAs increases with decreasing cell size while the total FA intensity increases with increasing cell size; and (c) the FA intensity decreases substantially when cell contractility is curtailed.

Original languageEnglish (US)
Pages (from-to)1484-1510
Number of pages27
JournalJournal of the Mechanics and Physics of Solids
Volume56
Issue number4
DOIs
StatePublished - Apr 2008

Funding

VSD acknowledges support from the Leverhulme Trust, UK. M.M., R.M.M. and A.G.E. thank the Army Research Office for their support through a Multidisciplinary University Research Initiative program on “Bio-Mechanical Interfaces for Cell-Based Microsystems”, Prime Award No.: W911NF-04-1-071.

Keywords

  • Focal adhesions
  • Mechano-sensitivity
  • Myosin.
  • Self-assembly
  • Stress fibers

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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