A mechanochemical model of cell reorientation on substrates under cyclic stretch

PLoS One. 2013 Jun 6;8(6):e65864. doi: 10.1371/journal.pone.0065864. Print 2013.

Abstract

We report a theoretical study on the cyclic stretch-induced reorientation of spindle-shaped cells. Specifically, by taking into account the evolution of sub-cellular structures like the contractile stress fibers and adhesive receptor-ligand clusters, we develop a mechanochemical model to describe the dynamics of cell realignment in response to cyclically stretched substrates. Our main hypothesis is that cells tend to orient in the direction where the formation of stress fibers is energetically most favorable. We show that, when subjected to cyclic stretch, the final alignment of cells reflects the competition between the elevated force within stress fibers that accelerates their disassembly and the disruption of cell-substrate adhesion as well, and an effectively increased substrate rigidity that promotes more stable focal adhesions. Our model predictions are consistent with various observations like the substrate rigidity dependent formation of stable adhesions and the stretching frequency, as well as stretching amplitude, dependence of cell realignment. This theory also provides a simple explanation on the regulation of protein Rho in the formation of stretch-induced stress fibers in cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Cell Adhesion
  • Cell Shape
  • Cells, Cultured
  • Cytoskeleton / chemistry
  • Cytoskeleton / physiology*
  • Eukaryotic Cells / cytology*
  • Eukaryotic Cells / metabolism
  • Eukaryotic Cells / physiology
  • Focal Adhesions / chemistry
  • Focal Adhesions / physiology*
  • Humans
  • Models, Biological*
  • Stress Fibers / chemistry
  • Stress Fibers / physiology*
  • Stress, Mechanical
  • Thermodynamics
  • rho GTP-Binding Proteins / physiology*

Substances

  • rho GTP-Binding Proteins

Grants and funding

This work was supported from the “Thousand Young Talents Program” of China, the Fundamental Research Funds for Central Universities (Nos. 2012QNA4023 and 2011XZZX002) of China, the National Natural Science Foundation of China (No. 11202184), the Research Grants Council (Project No. HKU 7148/10E) of the Hong Kong Special Administration Region, as well as a seed fund (Project No. 201111159112) from the University of Hong Kong. H.G. also gratefully acknowledges support from the University of Hong Kong through the Distinguished Visiting Scholars Scheme (DVSS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.