Mechanical tugging force regulates the size of cell-cell junctions

Zhijun Liu, John L. Tan, Daniel M. Cohen, Michael T. Yang, Nathan J. Sniadecki, Sami Alom Ruiz, Celeste M. Nelson, Christopher S. Chen

Research output: Contribution to journalArticle

444 Scopus citations

Abstract

Actomyosin contractility affects cellular organization within tissues in part through the generation of mechanical forces at sites of cell-matrix and cell-cell contact. While increased mechanical loading at cell-matrix adhesions results in focal adhesion growth, whether forces drive changes in the size of cell-cell adhesions remains an open question. To investigate the responsiveness of adherens junctions (AJ) to force, we adapted a system of microfabricated force sensors to quantitatively report cell-cell tugging force and AJ size. We observed that AJ size was modulated by endothelial cell-cell tugging forces: AJs and tugging force grew or decayed with myosin activation or inhibition, respectively. Myosin-dependent regulation of AJs operated in concert with a Rac1, and this coordinated regulation was illustrated by showing that the effects of vascular permeability agents (S1P, thrombin) on junctional stability were reversed by changing the extent to which these agents coupled to the Rac and myosin-dependent pathways. Furthermore, direct application of mechanical tugging force, rather than myosin activity per se, was sufficient to trigger AJ growth. These findings demonstrate that the dynamic coordination of mechanical forces and cell-cell adhesive interactions likely is critical to the maintenance of multicellular integrity and highlight the need for new approaches to study tugging forces.

Original languageEnglish (US)
Pages (from-to)9944-9949
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number22
DOIs
StatePublished - Jun 1 2010

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Adherens junction
  • Mechanotransduction
  • Myosin
  • PDMS
  • Traction force

Fingerprint Dive into the research topics of 'Mechanical tugging force regulates the size of cell-cell junctions'. Together they form a unique fingerprint.

  • Cite this