UC San Diego

Human mesenchymal stem cell (hMSC) differentiation has been shown to depend in part on extracellular matrix stiffness, however, the mechanotransduction pathways which must be responsible are largely unknown. Several candidate mechanosensors were identified and screened based on kinase binding accessibility, yielding five likely mechanotransducers. Of these five, only one, SORBS1, was shown to be necessary for osteogenic differentiation but not myogenic differentiation. MAPK1 inhibition seems to have similar effects on osteogenic differentiation as SORBS1 knockdown. Additionally, SORBS1 is immonuprecipitated with MAPK1 in an extracellular- stiffness-dependent manner. These data suggest that SORBS1 is a force-sensitive adhesion protein partly responsible for regulating stem cell fate