Model for the alignment of actin filaments in endothelial cells subjected to fluid shear stress

Abstract

Cultured vascular endothelial cells undergo significant morphological changes when subjected to sustained fluid shear stress. The cells elongate and align in the direction of applied flow. Accompanying this shape change is a reorganization at the intracellular level. The cytoskeletal actin filaments reorient in the direction of the cells' long axis. How this external stimulus is transmitted to the endothelial cytoskeleton still remains unclear. In this article, we present a theoretical model accounting for the cytoskeletal reorganization under the influence of fluid shear stress. We develop a system of integro-partial-differential equations describing the dynamics of actin filaments, the actin-binding proteins, and the drift of transmembrane proteins due to the fluid shear forces applied on the plasma membrane. Numerical simulations of the equations show that under certain conditions, initially randomly oriented cytoskeletal actin filaments reorient in structures parallel to the externally applied fluid shear forces. Thus, the model suggests a mechanism by which shear forces acting on the cell membrane can be transmitted to the entire cytoskeleton via molecular interactions alone.

Spatiotemporal Analysis of Flow-Induced Intermediate Filament Displacement in Living Endothelial Cells

“…Whereas previous studies have measured average cytoskeletal strain using internalized microsphere markers (Simon and Schmid-Schönbein, 1990;Caille et al, 1998), 4-D GFP-vimentin fluorescence allows measurement of network strain distribution directly from IF positions. The computation of flow-induced cytoskeletal network strain has several important implications for understanding cellular biomechanics, as suggested by theoretical modeling of a shear stress influence on actin dynamics (Suciu et al, 1997). Prediction of fluid shear force distribution on the endothelial surface has been computed from topographical maps measured by atomic force microscopy (Barbee et al, 1995).…”

Response of an actin filament network model under cyclic stretching through a coarse grained Monte Carlo approach

“…A major and minor x' and y' axes was then defined on this ellipse. Because cellular orientation is a predictor of actin filament orientation (Suciu et al , 1997; Swailes et al , 2004), we then quantified actin filament orientation by comparing the ellipse major axis orientation to the direction of uniaxial stretch. Only cells whose actin filaments exhibited a single orientation were used for analysis.…”

Upregulation of immunoreactivity of endothelin‐1 and α‐SMA in PDL microvasculature following acute tooth loading: an immunohistochemical study in the marmoset

“…Studies of vascular endothelial cell loading, such as experimental cyclic mechanical stretching, reveal remodelling of their actin cytoskeleton (14). Sustained, induced fluid shear stress (17) and normal haemodynamic forces also affect endothelial cell morphology and function, including reorganization of the cytoskeletal actin filaments. Fluid shear stress presumably acts through the endothelial cell membrane, via membrane spanning integrin glycoproteins, to cause significant intracellular morphological changes.…”