Mechano-topographic modulation of stem cell nuclear shape on nanofibrous scaffolds.

Stem cells transit along a variety of lineage-specific routes towards differentiated phenotypes. These fate decisions are dependent not just on the soluble chemical cues that are encountered or enforced in vivo and in vitro, but also on physical cues from the cellular microenvironment. These physical cues can consist of both nano- and micro-scale topographical features, as well as mechanical inputs provided passively (from the base properties of the materials to which they adhere) or actively (from extrinsic applied mechanical deformations). A suitable tool to investigate the coordination of these cues lies in nanofibrous scaffolds, which can both dictate cellular and cytoskeletal orientation and facilitate mechanical perturbation of seeded cells. Here, we demonstrate a coordinated influence of scaffold architecture (aligned vs. randomly organized fibers) and tensile deformation on nuclear shape and orientation. Sensitivity of nuclear morphology to scaffold architecture was more pronounced in stem cell populations than in terminally differentiated fibrochondrocytes. Tension applied to the scaffold elicited further alterations in nuclear morphology, greatest in stem cells, that were mediated by the filamentous actin cytoskeleton, but not the microtubule or intermediate filament network. Nuclear perturbations were time and direction dependent, suggesting that the modality and direction of loading influenced nuclear architecture. The present work may provide additional insight into the mechanisms by which the physical microenvironment influences cell fate decisions, and has specific application to the design of new materials for regenerative medicine applications with adult stem cells.