A Role for Integrin-ECM Bonds as Mechanotransducers that Modulate Adult Stem Cell Fate

Abstract

Mesenchymal stem cells (MSC), occasionally referred to as “adult stem cells,” are a multipotent cell population derived from bone marrow. MSC are an important cell population from therapeutic and fundamental science perspectives, and thus have been studied extensively. In particular, there has been substantial focus on using biomaterials to control the fate of these cells in the context of tissue regeneration. In this chapter, we review evidence for the role of substrate mechanical properties (and elastic modulus in particular) in regulating MSC fate in 2D and 3D cultures in vitro. Importantly, MSC fate appears to be markedly sensitive to the elasticity of the micro-environment in both cases, but mechanisms proposed for cellular mechanosensitivity that were based on 2D culture – in particular, a focus on morphological change as a means for sensing and responding to substrate mechanics – appear to be insufficient to explain MSC responses to substrate mechanics in 3D culture. Instead, we present recent evidence that molecular-scale changes in the cell-material interface, even absent gross morphology changes in cells, are consistent with cell fate changes in both 2D and 3D cultures. Remarkably, the mechanical interplay between cell traction forces and the material resisting this traction has both quantitative effects on occupancy of integrin adhesion receptors, as well as qualitative effects on which integrins are used for adhesion. The possibility that this is due to catch-bonds forming between integrins and materials is discussed, along with other explanations derived from the recent literature. Finally, an overview of the implications of these results for the fields of mechanotransduction and biomaterials engineering is presented.