Matrix stiffness changes affect astrocyte phenotype in an in vitro injury model

Abstract Injury to the central nervous system (CNS) usually leads activation of astrocytes, followed by glial scar formation. The formation scars from active astrocytes in vivo has been found be dependent on cell microenvironment. However, how respond different microenvironmental cues during formation, such as changes matrix stiffness, remains elusive. In this work, we established an vitro model assess responses stiffness that may related pathophysiology. investigated hydrogel backbones are composed collagen type I and alginate. these hybrid hydrogels can dynamically changed association or dissociation alginate chains through adding crosslinkers calcium chloride a decrosslinker sodium citrate, respectively. We obtain phenotypes when cultured stiffnesses. obtained switched situ changing presence cells. Specifically, stiffening reverts astrogliosis, whereas softening initiates astrocytic 3D. Moreover, effect is mediated Yes-associated protein (YAP), where YAP inhibition enhances upregulation GFAP contributes astrogliosis. To investigate underlying mechanism stiffness-dependent expression, also developed mathematical describe time-dependent dynamics biomolecules involved mechanotransduction process astrocytes. modeling results further indicate fate behavior cytoskeleton subsequent activity YAP. study will guide researchers re-examine role reactive astrogliosis inspire development novel therapeutic approach for controlling following injury, enabling axonal regrowth improving functional recovery exploiting benefits mechanobiology studies.