Mechanical tugging force regulates the size of cell–cell junctions

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

Competition between human cells by entosis

“…The force imbalance alone could be sufficient to further activate myosin II contractility and promote entosis [28,29]. The activation of RhoA in one cell of a pair, or introduction of phosphomimetic MLC, has been shown to induce growth of adherens junction as a result of increased tugging force by actomyosin [30]. Here, we show a similar effect of tension imbalance that promotes junctional growth that is sufficient to enwrap an entire cell.…”

Endothelial basement membrane laminin 511 is essential for shear stress response

“…The maintenance and stability of cell–cell junctions is regulated by the balance of cell–cell adhesion and cellular contractility (Liu et al , 2010; Yamamoto et al , 2015). We therefore compared the level of phosphorylated myosin light chain II (pMLC II) in WT, Tek‐Cre::Lama5 −/− and Lama4 −/− mesenteric resistance arteries as a measure of actomyosin contractility (van Nieuw Amerongen et al , 2007; Abraham et al , 2009).…”

Spatial coordination between cell and nuclear shape within micropatterned endothelial cells

“…In contrast, treatment with blebbistatin, which inhibits actomyosin contractility, and latrunculin A, which results in reduced F-actin and focal adhesion (FA) assembly, caused a significant rounding of the nucleus (NSI = 0.91 ± 0.05 and 0.94 ± 0.03, respectively), suggesting that actomyosin activity is a key component of the nuclear deformation process. Finally, we studied the response of thrombin, a vascular permeability agent, which was observed to induce a fast retraction of ECs through increased RhoA-mediated myosin-generated contraction 31,32 . Remarkably, thrombin treatment resulted in larger deformation of the nucleus (NSI = 0.56 ± 0.04, Fig.…”