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A mechanochemical model of cell reorientation on substrates under cyclic stretch.

Qian J, Liu H, Lin Y, Chen W, Gao H - PLoS ONE (2013)

Bottom Line: We report a theoretical study on the cyclic stretch-induced reorientation of spindle-shaped cells.Our main hypothesis is that cells tend to orient in the direction where the formation of stress fibers is energetically most favorable.This theory also provides a simple explanation on the regulation of protein Rho in the formation of stretch-induced stress fibers in cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Engineering Mechanics, Soft Matter Research Center, Zhejiang University, Hangzhou, Zhejiang, China.

ABSTRACT
We report a theoretical study on the cyclic stretch-induced reorientation of spindle-shaped cells. Specifically, by taking into account the evolution of sub-cellular structures like the contractile stress fibers and adhesive receptor-ligand clusters, we develop a mechanochemical model to describe the dynamics of cell realignment in response to cyclically stretched substrates. Our main hypothesis is that cells tend to orient in the direction where the formation of stress fibers is energetically most favorable. We show that, when subjected to cyclic stretch, the final alignment of cells reflects the competition between the elevated force within stress fibers that accelerates their disassembly and the disruption of cell-substrate adhesion as well, and an effectively increased substrate rigidity that promotes more stable focal adhesions. Our model predictions are consistent with various observations like the substrate rigidity dependent formation of stable adhesions and the stretching frequency, as well as stretching amplitude, dependence of cell realignment. This theory also provides a simple explanation on the regulation of protein Rho in the formation of stretch-induced stress fibers in cells.

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Long-time average filament density  as a function of the cell orientation angle  under a 10% stretch at different frequencies.(a) . (b)  where strain stiffening is not present as the substrate is stretched. (c, d) Effects of (c) strain stiffening and (d) substrate rigidity on  for low frequencies (0.05 Hz and 0.001 Hz, respectively).
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pone-0065864-g007: Long-time average filament density as a function of the cell orientation angle under a 10% stretch at different frequencies.(a) . (b) where strain stiffening is not present as the substrate is stretched. (c, d) Effects of (c) strain stiffening and (d) substrate rigidity on for low frequencies (0.05 Hz and 0.001 Hz, respectively).

Mentions: If we denote as the long-time average value of , Fig. 7a plots as a function of orientation angle , and also shows how varies with respect to when the stretching frequency is reduced from 1 Hz to 0.2 and 0.05 Hz. Obviously, stable SFs can be formed in all orientations when the stretching frequency is low enough, say below 0.05 Hz. Furthermore, under such circumstance, the maximum density of SFs is achieved when cells are aligned parallel to the stretch axis (), in direct contrast to cases where the stretching frequency is relatively high. Physically, this can be understood by realizing that contracting filaments have enough time to relax the imposed strain when is small and hence the force within them remains more or less unchanged at constant level . As such, the effect of stretch-induced hardening of substrate will outweigh that introduced by the elevation in filament force, eventually causing more FA bonds as well as more SFs to form. It is conceivable that cells prefer to orient in the direction where the densities of both SFs and FAs are maximized and consequently, the strongest cell-substrate attachment is achieved. If we accept this hypothesis, then Fig. 7a suggests that cells are more likely to align themselves along the stretching direction when the stretch is static or quasi-static, a prediction consistent with experimental observations [5], [6].


A mechanochemical model of cell reorientation on substrates under cyclic stretch.

Qian J, Liu H, Lin Y, Chen W, Gao H - PLoS ONE (2013)

Long-time average filament density  as a function of the cell orientation angle  under a 10% stretch at different frequencies.(a) . (b)  where strain stiffening is not present as the substrate is stretched. (c, d) Effects of (c) strain stiffening and (d) substrate rigidity on  for low frequencies (0.05 Hz and 0.001 Hz, respectively).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675090&req=5

pone-0065864-g007: Long-time average filament density as a function of the cell orientation angle under a 10% stretch at different frequencies.(a) . (b) where strain stiffening is not present as the substrate is stretched. (c, d) Effects of (c) strain stiffening and (d) substrate rigidity on for low frequencies (0.05 Hz and 0.001 Hz, respectively).
Mentions: If we denote as the long-time average value of , Fig. 7a plots as a function of orientation angle , and also shows how varies with respect to when the stretching frequency is reduced from 1 Hz to 0.2 and 0.05 Hz. Obviously, stable SFs can be formed in all orientations when the stretching frequency is low enough, say below 0.05 Hz. Furthermore, under such circumstance, the maximum density of SFs is achieved when cells are aligned parallel to the stretch axis (), in direct contrast to cases where the stretching frequency is relatively high. Physically, this can be understood by realizing that contracting filaments have enough time to relax the imposed strain when is small and hence the force within them remains more or less unchanged at constant level . As such, the effect of stretch-induced hardening of substrate will outweigh that introduced by the elevation in filament force, eventually causing more FA bonds as well as more SFs to form. It is conceivable that cells prefer to orient in the direction where the densities of both SFs and FAs are maximized and consequently, the strongest cell-substrate attachment is achieved. If we accept this hypothesis, then Fig. 7a suggests that cells are more likely to align themselves along the stretching direction when the stretch is static or quasi-static, a prediction consistent with experimental observations [5], [6].

Bottom Line: We report a theoretical study on the cyclic stretch-induced reorientation of spindle-shaped cells.Our main hypothesis is that cells tend to orient in the direction where the formation of stress fibers is energetically most favorable.This theory also provides a simple explanation on the regulation of protein Rho in the formation of stretch-induced stress fibers in cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Engineering Mechanics, Soft Matter Research Center, Zhejiang University, Hangzhou, Zhejiang, China.

ABSTRACT
We report a theoretical study on the cyclic stretch-induced reorientation of spindle-shaped cells. Specifically, by taking into account the evolution of sub-cellular structures like the contractile stress fibers and adhesive receptor-ligand clusters, we develop a mechanochemical model to describe the dynamics of cell realignment in response to cyclically stretched substrates. Our main hypothesis is that cells tend to orient in the direction where the formation of stress fibers is energetically most favorable. We show that, when subjected to cyclic stretch, the final alignment of cells reflects the competition between the elevated force within stress fibers that accelerates their disassembly and the disruption of cell-substrate adhesion as well, and an effectively increased substrate rigidity that promotes more stable focal adhesions. Our model predictions are consistent with various observations like the substrate rigidity dependent formation of stable adhesions and the stretching frequency, as well as stretching amplitude, dependence of cell realignment. This theory also provides a simple explanation on the regulation of protein Rho in the formation of stretch-induced stress fibers in cells.

Show MeSH
Related in: MedlinePlus