Prediction of Cell Alignment on Cyclically Strained Grooved Substrates

Abstract

Cells respond to both mechanical and topographical stimuli by reorienting and reorganizing their cytoskeleton. Under certain conditions, such as for cells on cyclically stretched grooved substrates, the effects of these stimuli can be antagonistic. The biophysical processes that lead to the cellular reorientation resulting from such a competition are not clear yet. In this study, we hypothesized that mechanical cues and the diffusion of the intracellular signal produced by focal adhesions are determinants of the final cellular alignment. This hypothesis was investigated by means of a computational model, with the aim to simulate the (re)orientation of cells cultured on cyclically stretched grooved substrates. The computational results qualitatively agree with previous experimental studies, thereby supporting our hypothesis. Furthermore, cellular behavior resulting from experimental conditions different from the ones reported in the literature was simulated, which can contribute to the development of new experimental designs.

Modelling The Combined Effects Of Collagen and Cyclic Strain On Cellular Orientation In Collagenous Tissues

“…The first hypothesis, contact guidance, is motivated by experimental studies that have shown that cells are able to respond to topographical cues by (re)adjusting their orientation. For example, it has been observed that cells cultured on microgrooved substrates tend to align along the direction of these grooves 35 – 37 and that these patterns can restrict the reorientation capacity of cells in response to cyclic strain 38 – 40 . Collagen seems to provide cells with analogous stimuli 7 , 14 , 41 , 42 .…”

“…Thus, this computational algorithm could in principle serve to model and simulate also the behaviour of cells in dynamically loaded collagenous tissues. Compared to the phenomenological approach proposed in the present study, the previous approach 40 has the advantage of being based on thermodynamics. However, adopting the same theory and approach to simulate cells in cyclically stretched collagen gels is in practice impossible because of excessive computational costs.…”

“…In one of our previous studies 40 , we proposed a computational approach based on thermodynamics to simulate the remodeling and interaction of stress fibers and focal adhesion signalling for cells on cyclically strained grooved surfaces. On such surfaces, cells respond to both mechanical and topographical stimuli.…”

A modeling framework for electro-mechanical interaction between excitable deformable cells

“…Though our modeling refers to the cell micro-scale, we assume a continuum approach [30]. Experimental evidences on single cell contractility showed that forces are induced where no visible stress fibers are present, thus implying that a much finer scale is responsible for the observed phenomena and therefore continuum level considerations can be adopted [27,32,33,34].Structural and physical properties of contact myocytes, in particular, will be the main object of this study. Intercellular communication between excitable contractile cells concentrates at the intercaleted discs and concerns with microscopic electrical conductance, metabolic and mechanical coupling [35].…”

“…Though our modeling refers to the cell micro-scale, we assume a continuum approach [30]. Experimental evidences on single cell contractility showed that forces are induced where no visible stress fibers are present, thus implying that a much finer scale is responsible for the observed phenomena and therefore continuum level considerations can be adopted [27,32,33,34].…”