Cell mechanosensitivity is enabled by the LINC nuclear complex

Sensation of the mechanical qualities of the environment is critical in directing cellular function and, in the case of stem cells, regulating lineage selection. This seminar will focus on the identification of mechanical factors regulating mesenchymal stem cells in the bone marrow that provide regenerative capacity by replacing and reinforcing the skeleton at load bearing sites. The ability of mesenchymal stem cells to respond to mechanical cues generated during functional loading is critical for this capacity. The importance of the physical connections between the nucleus and the cellular cytoskeleton has become increasingly apparent in recent years as the loss of nuclear integrity underlies the etiology of clinically significant premature aging and muscle-wasting disorders. I will discuss my findings that how mechanical coupling of nucleus with the cytoskeleton contributes to mesenchymal stem cell mechanosensitivity and fate selection. During the talk I will further highlight major research themes we are pursuing towards understanding cellular and tissue level mechanical adaptations, as well as strategies for treatment and rehabilitation of musculoskeletal impairments at the cellular level.