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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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Evolutions of the bond and filament densities.(a) A relatively stiff substrate of . (b) A relatively soft substrate of .
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pone-0065864-g005: Evolutions of the bond and filament densities.(a) A relatively stiff substrate of . (b) A relatively soft substrate of .

Mentions: By choosing initial conditions as and , the dynamic evolutions of and when are shown in Figs. 5a and 5b, for and 1.1 respectively. Related to biological aspects, the nonzero initial value of is considered to arise from nascent nucleation of focal complex that may or may not lead to mature FAs and associated SFs, as discussed in previous sections. Clearly, the steady state solution given by Eq. (12) can indeed be achieved when is relatively small, or equivalently when the substrate is more rigid. However, as the substrate becomes more compliant, the steady state solution becomes unstable when , that is any tiny fluctuations will cause the bond, as well as the contracting filament, density to suddenly drop to zero, referring to Fig. 5b. Notice that roughly corresponds to a substrate with rigidity around ∼15 kPa. Interestingly, it has been reported that both normal rat kidney (NRK) epithelial and 3T3 fibroblastic cells cannot form stable FAs on substrates with modulus less than ∼10 kPa, while these cells can firmly attach to substrates with stiffness of ∼60 kPa and above [2], in broad agreement with the theoretical predictions here. We have to point out that similar conclusion has also been obtained recently by Paszek and co-workers [26], who showed that clustering of integrins, a key step in the formation of stable adhesion clusters, is greatly impaired when the substrate is softer than a threshold value.


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

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

Evolutions of the bond and filament densities.(a) A relatively stiff substrate of . (b) A relatively soft substrate of .
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065864-g005: Evolutions of the bond and filament densities.(a) A relatively stiff substrate of . (b) A relatively soft substrate of .
Mentions: By choosing initial conditions as and , the dynamic evolutions of and when are shown in Figs. 5a and 5b, for and 1.1 respectively. Related to biological aspects, the nonzero initial value of is considered to arise from nascent nucleation of focal complex that may or may not lead to mature FAs and associated SFs, as discussed in previous sections. Clearly, the steady state solution given by Eq. (12) can indeed be achieved when is relatively small, or equivalently when the substrate is more rigid. However, as the substrate becomes more compliant, the steady state solution becomes unstable when , that is any tiny fluctuations will cause the bond, as well as the contracting filament, density to suddenly drop to zero, referring to Fig. 5b. Notice that roughly corresponds to a substrate with rigidity around ∼15 kPa. Interestingly, it has been reported that both normal rat kidney (NRK) epithelial and 3T3 fibroblastic cells cannot form stable FAs on substrates with modulus less than ∼10 kPa, while these cells can firmly attach to substrates with stiffness of ∼60 kPa and above [2], in broad agreement with the theoretical predictions here. We have to point out that similar conclusion has also been obtained recently by Paszek and co-workers [26], who showed that clustering of integrins, a key step in the formation of stable adhesion clusters, is greatly impaired when the substrate is softer than a threshold value.

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