Model of cellular mechanotransduction via actin stress fibers

Abstract

Mechanical stresses due to blood flow regulate vascular endothelial cell structure and function and play a key role in arterial physiology and pathology. In particular, the development of atherosclerosis has been shown to correlate with regions of disturbed blood flow where endothelial cells are round and have a randomly organized cytoskeleton. Thus, deciphering the relation between the mechanical environment, cell structure and cell function is a key step towards understanding the early development of atherosclerosis. Recent experiments have demonstrated very rapid (∼100 msec) and long-distance (∼10 µm) cellular mechanotransduction in which prestressed actin stress fibers play a critical role. Here, we develop a model of mechanical signal transmission within a cell by describing strains in a network of prestressed viscoelastic stress fibers following the application of a force to the cell surface. We find force transmission dynamics that are consistent with experimental results. We also show that the extent of stress fiber alignment and the direction of the applied force relative to this alignment are key determinants of the efficiency of mechanical signal transmission. These results are consistent with the link observed experimentally between cytoskeletal organiza- tion, mechanical stress, and cellular responsiveness to stress. Based on these results, we suggest that mechanical strain of actin stress fibers under force constitutes a key link in the mechanotransduction chain.

Modeling Stem Cell Myogenic Differentiation

“…They include analyses of spreading on patterned substrates1, alignment under cyclic load23, mechanotransduction under applied shear forces4, deformation under 3-D flow forces5, force generation with 3-D tissue6, etc. However, the modeling of stem cell mechanobiology, where mechanotransduction converges with cell differentiation, remains less developed.…”

Mechanotransmission in endothelial cells subjected to oscillatory and multi-directional shear flow

“…The multi-directional and pulsatile flow regimes significantly reduce stresses in the highest SFs (figure 4c-f ). Time constants of mechanical stimulus transmission have been shown to play an important role in determining the dynamics of cellular responsiveness to mechanical stimulation [37][38][39][40]]. The present model tested and quantified this role.…”

“…2) is applied to the normal stresses of a viscoelastic material. The relaxation time, t*, is defined as [37,39]:…”

“…The model of Dabagh et al [12] treated all cellular components as incompressible neo-Hookean materials; viscoelastic effects were not considered. Gouget et al [37] developed a model of mechanical signal transmission within a cell by describing strains in a network of pre-stressed viscoelastic stress fibres following the application of a force to the cell surface. Barakat [38] developed a mathematical model for the shear stressdeformation of a flow sensor on the EC surface which was modelled with a viscoelastic formulation.…”

An integrated enhancement and reconstruction strategy for the quantitative extraction of actin stress fibers from fluorescence micrographs

“…For example, order parameters analysis has been used to describe the aggregate image texture and orientation, without explicit treatment of each discrete stress fibers [38], thus avoiding the challenging task of detecting and segmenting individual filaments. Alternatively, a simulation-based approach can be used to study the stress fiber networks based on Finite Element analysis of idealized cellular architectures [12, 40–45]. Likewise, stress fiber networks can be treated as a micrograph-based linear superposition of filaments such that relevant coefficients can be solved by linear optimization [40].…”