Cell contractility facilitates alignment of cells and tissues to static uniaxial stretch

Abstract

During animal development and homeostasis, the structure of tissues, including muscles, blood vessels and connective tissues adapts to mechanical strains in the extracellular matrix (ECM). These strains originate from the differential growth of tissues or forces due to muscle contraction or gravity. Here we show using a computational model that by amplifying local strain cues, active cell contractility can facilitate and accelerate the reorientation of single cells to static strains. At the collective cell level, the model simulations show that active cell contractility can facilitate the formation of strings along the orientation of stretch. The computational model is based on a hybrid cellular Potts and finite-element simulation framework describing a mechanical cell-substrate feedback, where: 1) cells apply forces on the ECM, such that 2) local strains are generated in the ECM, and 3) cells preferentially extend protrusions along the strain orientation. In accordance with experimental observations, simulated cells align and form string-like structures parallel to static uniaxial stretch. Our model simulations predict that the magnitude of the uniaxial stretch and the strength of the contractile forces regulate a gradual transition between string-like patterns and vascular network-like patterns. Our simulations also suggest that at high population densities, less cell cohesion promotes string formation.

arXiv comment24 pages, 6 figures; 12 pages of supplementary information with 11 supplementary figures and 2 supplementary tables

References in corpus (7)

• Strain-induced alignment in collagen gels
• Cell organization in soft media due to active mechanosensing
• Mechanical cell-matrix feedback explains pairwise and collective endothelial cell behavior in vitro
• Dynamics of Cell Shape and Forces on Micropatterned Substrates Predicted by a Cellular Potts Model
• Effect of Poisson ratio on cellular structure formation
• Vascular networks due to dynamically arrested crystalline ordering of elongated cells
• Collective effects in cellular structure formation mediated by compliant environments: a Monte Carlo study

Cited by in corpus (1)

• Designing Optimal Scaffold Topographies to Promote Nucleus-Guided Mechanosensitive Cell Migration Using in Silico Models