Zhijun Liu a,1, John L. Tan b,1, Daniel M. Cohen a,1, Michael T. Yang a, Nathan J. Sniadecki a, Sami Alom Ruiz a, Celeste M. Nelson b, and Christopher S. Chen a,b,2
-Author Affiliations
aDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104; and
bDepartment of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205
Edited by Shu Chien, University of California, San Diego, La Jolla, CA, and approved March 31, 2010 (received for review December 17, 2009)
↵1Z.L., J.L.T., and D.M.C. contributed equally to this paper.
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.
adherens junction mechanotransduction myosin PDMS traction force
Footnotes
2To whom correspondence should be addressed. E-mail:chrischen@seas.upenn.edu.
Author contributions: Z.L., J.L.T., D.M.C., M.T.Y., S.A.R., C.M.N., and C.S.C. designed research; Z.L., J.L.T., D.M.C., M.T.Y., and S.A.R. performed research; Z.L., J.L.T., D.M.C., M.T.Y., and C.M.N. contributed new reagents/analytic tools; Z.L., J.L.T., D.M.C., M.T.Y., and S.A.R. analyzed data; and Z.L., D.M.C., N.J.S., and C.S.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at
+++++
