Cell organization in soft media due to active mechanosensing.
Adhering cells actively probe the mechanical properties of their environment and use the resulting information to position and orient themselves. We show that a large body of experimental observations can be consistently explained from one unifying principle, namely that cells strengthen contacts and cytoskeleton in the direction of large effective stiffness. Using linear elasticity theory to model the extracellular environment, we calculate optimal cell organization for several situations of interest and find excellent agreement with experiments for fibroblasts, both on elastic substrates and in collagen gels: cells orient in the direction of external tensile strain; they orient parallel and normal to free and clamped surfaces, respectively; and they interact elastically to form strings. Our method can be applied for rational design of tissue equivalents. Moreover, our results indicate that the concept of contact guidance has to be reevaluated. We also suggest that cell-matrix contacts are up-regulated by large effective stiffness in the environment because, in this way, build-up of force is more efficient.
Bischofs
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IB
Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.
Schwarz
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US
D002448:Cell Adhesion; D003094:Collagen / Q000737:chemistry; D003599:Cytoskeleton / Q000737:chemistry / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D015233:Models, Statistical; D008962:Models, Theoretical; D009010:Monte Carlo Method; D015854:Up-Regulation
D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003094:Collagen