The position and size of individual focal adhesions are determined by intracellular stress‐dependent positive regulation

Abstract

It remains unclear how the subcellular positions and sizes of individual focal adhesions (FAs) are determined in stationary cells. The elucidation of spatial regulation mechanisms is important for accurate understanding of the cellular response to mechanical stress. Through a theoretical analysis on previously reported cell behavior, the present study demonstrates a close correlation between the appearances of mechanosensitive elements and intracellular stress reflecting traction stress that the cell exerts on the substrate. The magnitude and distribution of stress were predicted in this analysis by mimicking intrinsic actomyosin contraction independent of extracellular stimuli. Positions of FAs and actin stress fibers corresponded to the local maximum and minimum stress points, respectively, and thus were determined by the global configuration of cell adhesions. Furthermore, their subcellular sizes were in agreement with the predicted stress magnitudes that were dependent on the local mechanical environment. These results suggest that a positive regulation (i.e., force and cell adhesion enhance each other) functions in the organization of individual FAs in nonmigrating cells.

Mechanosensing through focal adhesion‐anchored intermediate filaments

“…Actomyosin‐generated tension has been shown to be a major regulator of FAK and many other adhesion‐associated signaling molecules (5). To understand how vimentin filaments and their targeting to FAs influence adhesion‐dependent signaling, we have adopted the actomyosin contraction model postulated by Deguchi et al (62). According to this model, strain will be generated within the actomyosin gel only if it is held in place by physical constraints ( Fig.…”

Effect of low oxygen conditions on matrix metalloproteinase-9 production of macrophages subjected to cyclic stretching: involvement of ERK and Rho kinase pathways

“…Since ERK acts as an upstream signal for HIF-1α expression (Mottet, et al, 2002) (Westra, et al, 2010), activation of ERK may occur under the 1% O 2 condition, which leads the increased productions of MMP-9 in the present study. We also have a result that the increases in MMP-9 production by 1% O 2 were suppressed by the inhibition of Rho kinase, which is a downstream effector of the small GTPases Rho family RhoA and regulates actin cytoskeletal contractility via myosin light chain phosphorylation (Deguchi, et al, 2011). Previous studies have demonstrated that tension in actin cytoskeleton the Rho-Rho kinase pathway (McMurtry, et al, 2003) (Bailly, et al, 2004.…”

Formation of contractile networks and fibers in the medial cell cortex through myosin‐II turnover, contraction, and stress‐stabilization

“…Future work could examine this process in more detail as well as the individual actin and myosin filament sliding within the fiber and formation of sarcomeric structures [Yoshinaga et al, 2010;Friedrich et al, 2012;Stachowiak et al, 2012], processes that our model did not address. Such studies, together with our work can provide a link to cell-level dynamics that have so far been studied with coarse-graining at a more macroscopic level compared to our work [Stamenovic et al, 2009;Deguchi et al, 2011;Kaunas et al, 2011;Pirentis et al, 2011;Schwarz and Safran, 2013], mostly in the context of cell mechanosensing. Although our 2D model is simple, future extensions could be useful in modeling how elastic substrates of different stiffness develop cytoskeletal networks with different morphology and mechanical properties [Discher et al, 2005], and to investigate how the cytoskeletal network reorganizes in respond to external perturbations such as cyclic stretching [Hayakawa et al, 2001] or shear flow [Sakamoto et al, 2010].…”