Textured nanofibrils drive microglial phenotype

Abstract Microglia are highly plastic cells that change their properties in response to their microenvironment. By using immunofluorescence, live-cell imaging, electrophysiological recordings and RNA sequencing, we investigated the regulation of modified bacterial cellulose (mBC) nanofibril substrates on microglial properties. We demonstrate that mBC substrates induces ramified microglia with constantly extending and retracting processes, reminiscent of what is observed in vivo. Patch-clamp recordings showed that microglia acquire a more negative resting membrane potential and have increased inward rectifier K+ currents, caused by an upregulation of Kir2.1 channels. Transcriptome analysis shows upregulation of genes involved in the immune response and downregulation of genes linked to cell adhesion and cell motion. Furthermore, Arp2/3 complex activation and integrin-mediated signaling modulate microglial morphology and motility. Our studies demonstrate that mBC nanofibril substrates modulate microglial phenotype, paving the way for a microglia-material interface that may be very valuable for anti-neuroinflammatory drug screening.