The mechanosensitivity of cells, which determines how they are able to respond to mechanical signals received from their environment, is crucial for the functioning of all biological systems. However, a detailed understanding of such response is still lacking, as it involves processes occurring over a wide range of length- and time-scales. Experimentally, one of the preferred methods to investigate how crawling cells react to such stimulation is to apply cyclic stretching to the substrate to which they are attached. Studying the shape deformations and changes in motility, as well as the localization of characteristic proteins (e.g., actin or myosin) or the orientation of the actin filament network inside of the cell under stretching, has provided crucial information on their mechano-sensing abilities. In particular, cells have been shown to reorient under such perturbations, aligning at specific angles with respect to the stretching direction that depends strongly on the type of cell . We introduce a computation model for crawling cells on such periodically stretching substrates that is able to account for the complex shape deformations, the URLanization of the actin-network, and the coupling to the substrate . As in experiments, we are able to observe preferential alignment along perpendicular, parallel, or oblique angles to the stretching, depending on the frequency of stretching, as well as on the type of response exhibited by our model cells .
The mechanosensitivity of cells, which determines how they are able to respond to mechanical signals received from their environment, is crucial for the functioning of all biological systems. In experiments, cells placed on cyclically stretched substrates have been shown to reorient in a direction that depends not only on the type of cell , but also on the mechanical properties of the substrate, and the amplitude and rate of stretching. However, the underlying biochemical and mechanical mechanisms responsible for this realignment are still not completely understood. In this study, we introduce a computational model for fast crawling on cyclically stretched substrates that accounts for the sub-cellular processes responsible for the cell shape and motility, as well as the coupling to the substrate through the focal adhesion sites. In particular, we focus on the role of the focal adhesion dynamics, and show that the reorientation under cyclic stretching is strongly dependent on the frequency , as has been observed experimentally. Furthermore, we show that an asymmetry during the loading and unloading phases of the stretching, whether coming from the response of the cell itself, or from the stretching protocol, can be used to selectively align the cells in either the parallel or perpendicular directions .
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However, a detailed understanding of such response is still lacking, as it involves processes occurring over a wide range of length- and time-scales. Experimentally, one of the preferred methods to investigate how crawling cells react to such stimulation is to apply cyclic stretching to the substrate to which they are attached. Studying the shape deformations and changes in motility, as well as the localization of characteristic proteins (e.g., actin or myosin) or the orientation of the actin filament network inside of the cell under stretching, has provided crucial information on their mechano-sensing abilities. In particular, cells
In experiments, cells placed on cyclically stretched substrates
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under such perturbations, aligning at specific angles with respect to the stretching
in a
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strongly
not only
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. We introduce a computation model for crawling cells on such periodically stretching substrates that is able to account for the complex shape deformations, the URLanization of the actin-network, and the
, but also on the mechanical properties of the substrate, and the amplitude and rate of stretching. However, the underlying biochemical and mechanical mechanisms responsible for this realignment are still not completely understood. In this study, we introduce a computational model for fast crawling on cyclically stretched substrates that accounts for the sub-cellular processes responsible for the cell shape and motility, as well as the
R
. As in experiments, we are able to observe preferential alignment along perpendicular, parallel, or oblique angles to the stretching, depending
through the focal adhesion sites. In particular, we focus on the role of the focal adhesion dynamics, and show that the reorientation under cyclic stretching is strongly dependent
R
of stretching, as well as on the type of response exhibited by our model cells
, as has been observed experimentally. Furthermore, we show that an asymmetry during the loading and unloading phases of the stretching, whether coming from the response of the cell itself, or from the stretching protocol, can be used to selectively align the cells in either the parallel or perpendicular directions