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, 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.

Automated summary

Pathology-mimetic M-nanofibrils are shown to act as a defense mechanism to restore tissue homeostasis by manipulating immunological response, in contrast to physiology-mimetic P-nanofibrils. M-chirality displays higher affinity to cellular binding, inducing higher cellular contractile stress and activating mechanosensitive ion channel PIEZO1 to conduct Ca2+ influx, leading to biased nuclear transfer of STAT and promoting M2 polarization. These findings provide insights into the structural mechanisms of disease and suggest potential design basis for immunotherapy using bionic functional materials.