Size and shape matter: Role of surface curvature in inflammasome activation by synthetic microparticles (136.39)

Abstract

Abstract The human immune system is poised to recognize and respond to foreign particulate substances, like crystals, pollen, bacteria or fungal spores. While some particles can induce significant inflammation others are relatively non-inflammatory. The physical and chemical characteristics that determine the response to different particles are unclear. In this study, we sought to systematically examine the roles that particle size, shape, and surface texturing play in uptake efficiency and subsequent immune cell activation. Using a novel micro-capillary flow focusing technique, we generated microparticles of similar composition but varying in shape from spherical to budding. We discovered that particles with high surface curvature (budding particles) were associated with and phagocytosed by macrophages at higher frequency than particles with low surface curvature, i.e., smooth particles. Remarkably, budding particles also induced stronger IL-1β secretion than smooth particles, through activation of the Nalp3 inflammasome-signaling complex. In vivo, budding particles induced more rapid neutrophil recruitment to the injection site, a hallmark of acute inflammation, than spherical particles. Although currently underappreciated, these findings demonstrate a remarkable and pronounced role for particle shape and surface curvature, independent of chemical composition and surface ligand recognition, in immune cell activation.