Matrix Stiffness Regulates Glial Cell Morphology and Differentiation

MATRIX STIFFNESS REGULATES GLIAL CELL MORPHOLOGY AND DIFFERENTIATION By Mateusz M. Urbanski Advisor: Carmen Melendez-Vasquez Studies from our laboratory have shown that inhibition of non-muscle myosin II (NMII) activity has opposite effects on the formation of myelin by oligodendrocytes (OL), the myelinating glia of the central nervous system (CNS) and Schwann cells (SC), which perform the same function in the peripheral nervous system (PNS). The decrease of NMII activity in SC impairs their ability to establish polarity and myelinate, while its inhibition in OL enhances process branching and increases the amount of myelin formed in vitro an in vivo. A growing number of studies have shown that NMII also plays a role in the ability of cells to sense and respond to the stiffness of the surrounding extracellular matrix (ECM). In the PNS, the ECM consists of a dense SC-secreted basal lamina, which displays significantly higher rigidity than the more loosely organized CNS matrix. In order to evaluate whether the opposing effects of inhibiting NMII in glial cell differentiation and myelination are partly the result of NMII-mediated sensing of ECM stiffness, we have grown cultures of primary rat OL and SC on variable rigidity polyacrylamide matrices coated with covalently bound ECM proteins. We found that stiffer matrices inhibit OL branching as well as their expression of differentiation markers, and that these effects are correlated with