Mechanics of Microenvironment as Instructive Cues Guiding Stem Cell Behavior

Stem cells reside in a complex milieu during development, or in adult tissues, as well as in culture conditions. Their decision to differentiate, self-renew, or migrate is a result of an integrated response to extracellular stimuli, which are chemical, physical, and mechanical in nature. In recent years, research has shown that the mechanical properties of the microenvironment can regulate a variety of stem cell phenotypes by activating intracellular signal transduction leading to transcription. Many of these signaling pathways are primarily involved in mechanotransduction, suggesting that mechanical cues, particularly the rigidity and topographical architecture of the extracellular matrix directly regulate stem cell behavior. Novel bioengineering tools have made it possible for the first time to systematically and quantifiably understand the role of mechanical cues in stem cell biology. However, it is necessary to investigate activation of mechanotransduction in the context of other signals to which cells respond. How cells integrate complex presentation of signals, including mechanical cues, to formulate a decision will increase our understanding of fundamental stem cell biology, as well as inform future therapeutic applications in regenerative medicine.