The physiological chirality of extracellular environments is substantially affected by pathological diseases. However, how this stereochemical variation drives host immunity remains poorly understood. Here, it is reported that pathology-mimetic M-nanofibrils-but not physiology-mimetic P-nanofibrils-act as a defense mechanism that helps to restore tissue homeostasis by manipulating immunological response. Quantitative multi-omics in vivo and in vitro shows that M-nanofibrils significantly inhibit inflammation and promote tissue regeneration by upregulating M2 macrophage polarization and downstream immune signaling compared with P-nanofibrils. Molecular analysis and theoretical simulation demonstrate that M-chirality displays higher stereo-affinity to cellular binding, which induces higher cellular contractile stress and activates mechanosensitive ion channel PIEZOl to conduct Ca2+ influx. In turn, the nuclear transfer of STAT is biased by Ca2+ influx to promote M2 polarization. These findings underscore the structural mechanisms of disease, providing design basis for immunotherapy with bionic functional materials.
Keywords: chirality nanofibrils; immunological response; macrophage polarization.
© 2021 Wiley-VCH GmbH.