Chirality Bias Tissue Homeostasis By Manipulating Immunological Response.

The physiological chirality of extracellular environments is substantially affected by pathological diseases. However, how this stereochemical variation drives host immunity remains poorly understood. Here, we report 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 showed that M-nanofibrils significantly inhibited inflammation and promoted tissue regeneration by upregulating M2 macrophage polarization and downstream immune signaling compared with P-nanofibrils. Molecular analysis and theoretical simulation demonstrated that M-chirality displayed higher stereo-affinity to cellular binding, which induced higher cellular contractile stress and activated mechanosensitive ion channel PIEZOl to conduct Ca2+ influx. In turn, the nuclear transfer of STAT was 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. This article is protected by copyright. All rights reserved.