Substrate Compliance Directs the Osteogenic Lineages of Stem Cells from the Human Apical Papilla via the Processes of Mechanosensing and Mechanotransduction

ABSTRACT It is well recognized that the interaction between stem cells and their physical microenvironment plays a fundamental role in controlling cell behaviors and directing lineage commitment, which eventually determines cell fate. Any change in the physical characteristics of the extracellular matrix (ECM) in terms of topography, geometry and stiffness has a strong effect on this interaction. Nevertheless, the precise biomechanism that regulates the responses of stem cells to the biophysical properties of substrates is not fully understood. In this study, we generated a series of polydimethylsiloxane (PDMS) substrates with different stiffness properties and explored the whole process involved in the determination of osteogenic lineage in stem cells from the human apical papilla (hSCAPs) in response to substrate stiffness. We first found the hSCAPs responded to different substrate stiffnesses by changing their cell morphologies and cytoskeletons (via changes in α-tubulin and β-tubulin in microtubules a...