Limits...
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.

Show MeSH

Related in: MedlinePlus

The compliance of the bond-substrate system represented by the effective spring constant K.The receptors actually bind to specific head groups of certain adhesion molecules, such as fibronectin, coated on the substrate surface.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3675090&req=5

pone-0065864-g002: The compliance of the bond-substrate system represented by the effective spring constant K.The receptors actually bind to specific head groups of certain adhesion molecules, such as fibronectin, coated on the substrate surface.

Mentions: Note that the combined stiffness of the bond-substrate system is represented by the effective spring constant K. In other words, the bond is expected to displace by a distance once a force F is applied (Fig. 2). A simple scaling argument indicates that K can be expressed as(5)where is the diameter of the receptor (∼10 nm according to [38], [39]) and is the combined effective modulus of the substrate and the bond. One important feature about polymeric materials, as some of the soft substrates adopted in experiments [4]–[14], is that their rigidities generally increase with stretching, a phenomenon known as strain stiffening. For example, the moduli of reconstituted actin gels and fibroblasts have all been found to be nearly constant under small strains and increase with the applied strain following a simple power law of index ∼3/2 once the strain level is above a threshold value [40], [41]. Here in our model, is assumed to depend on the strain as [40](6)where is a critical strain on the order of a few percent, and is the modulus value for strains below . If the parameter exceeds the maximal stretch the substrate will experience, the material model in Eq. (6) reduces to the case of linear response without any effects of strain stiffening. In the following discussions, we will show that whether substrate stiffening is present or not may lead to distinct cellular responses to very slowly varying stretch, as revealed by several experiments [5]–[7], [15].


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

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

The compliance of the bond-substrate system represented by the effective spring constant K.The receptors actually bind to specific head groups of certain adhesion molecules, such as fibronectin, coated on the substrate surface.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065864-g002: The compliance of the bond-substrate system represented by the effective spring constant K.The receptors actually bind to specific head groups of certain adhesion molecules, such as fibronectin, coated on the substrate surface.
Mentions: Note that the combined stiffness of the bond-substrate system is represented by the effective spring constant K. In other words, the bond is expected to displace by a distance once a force F is applied (Fig. 2). A simple scaling argument indicates that K can be expressed as(5)where is the diameter of the receptor (∼10 nm according to [38], [39]) and is the combined effective modulus of the substrate and the bond. One important feature about polymeric materials, as some of the soft substrates adopted in experiments [4]–[14], is that their rigidities generally increase with stretching, a phenomenon known as strain stiffening. For example, the moduli of reconstituted actin gels and fibroblasts have all been found to be nearly constant under small strains and increase with the applied strain following a simple power law of index ∼3/2 once the strain level is above a threshold value [40], [41]. Here in our model, is assumed to depend on the strain as [40](6)where is a critical strain on the order of a few percent, and is the modulus value for strains below . If the parameter exceeds the maximal stretch the substrate will experience, the material model in Eq. (6) reduces to the case of linear response without any effects of strain stiffening. In the following discussions, we will show that whether substrate stiffening is present or not may lead to distinct cellular responses to very slowly varying stretch, as revealed by several experiments [5]–[7], [15].

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