Matrix Elasticity is sensed with Non-Muscle Myosin II and Directs Stem Cell Lineage Specification

摘要

Statement of Purpose: Many anchorage-dependent, contractile cell types respond to substrate elasticity, i.e. -Young's Modulus E, as sensitively as more well studied soluble or immobilized ligands, yet mechanisms by which cell-generated forces induce outside-in mechanical signals have been far less explored. Pluripotent cells, such as mesenchymal stem cells (MSCs), differentiate into a variety of connective tissues, including, nerve, muscle, and bone, that all have dramatically different microenvironments. Specifically, MSC lineage specification has only been studied via chemical stimuli or changes in cell shape and proliferation, yet current stem cell therapies in fibrotic tissue compared to normal tissue are limited by mechanical properties of the surrounding rigid matrix. Given the limited capacity for MSC differentiation in an extremely stiff matrix, we explored whether a range of substrate stiffnesses could drive MSC lineage specification.