Role of substrate biomechanics in controlling (stem) cell fate: Implications in regenerative medicine

Tissue-specific stem cells reside in a specialized environment known as the niche. The niche plays a central role in the regulation of cell behavior and, through the concerted action of soluble molecules, supportive somatic cells and extracellular matrix-components, directs stem cells to proliferate, differentiate or remain quiescent. Great efforts have been done to decompose and separately analyze the contribution of these cues in the in vivo environment. Specifically, the mechanical properties of the extracellular matrix influence many aspects of cell behavior, including self-renewal and differentiation. Deciphering the role of biomechanics could thereby provide important insights to control the stem cells responses in a more effective way with the aim to promote their therapeutic potential. In this review, we provide a wide overview of the effect that the microenvironment stiffness exerts on the control of cell behavior with a particular focus on the induction of stem cells differentiation. We also describe the process of mechanotransduction and the molecular effectors involved. Finally, we critically discuss the potential involvement of tissue biomechanics in the design of novel tissue engineering strategies.