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 induce ramified microglia with constantly extending and retracting processes, reminiscent of what is observed in vivo. Patch-clamp recordings show 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.

小胶质细胞是高度可塑性的细胞，可响应其微环境而改变其特性。通过使用免疫荧光，活细胞成像，电生理记录和RNA测序，我们研究了修饰的细菌纤维素（mBC）纳米原纤维底物对小胶质细胞特性的调控。我们证明，mBC底物诱导分枝的小胶质细胞不断扩展和缩回过程，让人联想到体内观察到的东西。膜片钳记录表明，小胶质细胞获得了更多的负静息膜电位，并增加了内向整流器K ⁺电流，由Kir2.1通道的上调引起。转录组分析显示与免疫反应有关的基因上调，与细胞粘附和细胞运动相关的基因下调。此外，Arp2 / 3复合物激活和整联蛋白介导的信号调节小胶质细胞形态和运动。我们的研究表明，mBC纳米原纤维底物调节小胶质细胞表型，为小胶质细胞-材料界面铺平了道路，这对于抗神经炎药物筛选可能非常有价值。