Textured nanofibrils drive microglial phenotype.

Qin Song, Simone Pifferi, Lin Shi, Chuntao Chen, Remo Proietti Zaccaria, Anna Menini, Jianping Cao, Qi Zhang, Vincent Torre

Journal: Biomaterials 2021;257():120177

PMID: 32682149

Full Text on Elsevier Science View on PubMed

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 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.

Address: International School for Advanced Studies (SISSA), Trieste, 34136, Italy; School of Pharmaceutical Engineering, Zhejiang Pharmaceutical College, Ningbo, Zhejiang, 315100, PR China; Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang, 315201, PR China.; International School for Advanced Studies (SISSA), Trieste, 34136, Italy; Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy.; School of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China.; Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang, 315201, PR China; Italian Institute of Technology, Genova, 16163, Italy.; International School for Advanced Studies (SISSA), Trieste, 34136, Italy.; School of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China. Electronic address: [email protected].; International School for Advanced Studies (SISSA), Trieste, 34136, Italy; School of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China; Joint Laboratory of Biophysics and Translational Medicine, ISM-SISSA, Suzhou, Jiangsu, 215123, PR China; Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang, 315201, PR China. Electronic address: [email protected].

DOI: 10.1016/j.biomaterials.2020.120177

Link outs

Subscription / membership required

Full Text Sources:

MeSH Terms: Membrane Potentials, Microglia, Phenotype, Signal Transduction, Up-Regulation