Mechanical control of stem cell differentiation using microengineered matrix

In this work, we explore the molecular mechanisms by which local mechanical properties (e.g., rigidity) of the extracellular matrix (ECM) cooperates with soluble cues to regulate lineage commitment of human mesenchymal stem cells (hMSCs). We have established different micropost array substrates that can definitively decouple matrix rigidity from other properties including adhesiveness. We applied these substrates to investigate the influences of matrix rigidity on cell adhesion, cytoskeleton assembly/contractility, cell spreading, and proliferation. We further show that matrix rigidity regulates commitment of hMSCs to either adipogenic or osteogenic fate: soft matrix facilitates adipogenic differentiation while stiff matrix proves osteogenic.