Jiang Shengjie, Zeng Qiang, Zhao Kai, Liu Jinying, Sun Qiannan, Huang Kang, He Ying, Zhang Xuehui, Wang Hui, Shi Xinghua, Feng Chuanliang, Deng Xuliang, Wei Yan
Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China.
Institute of Medical Technology, Peking University Health Science Center, Beijing, 100191, P. R. China.
Adv Mater. 2022 Jan;34(2):e2105136. doi: 10.1002/adma.202105136. Epub 2021 Oct 27.
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 Ca influx. In turn, the nuclear transfer of STAT is biased by Ca influx to promote M2 polarization. These findings underscore the structural mechanisms of disease, providing design basis for immunotherapy with bionic functional materials.
细胞外环境的生理手性会受到病理疾病的显著影响。然而，这种立体化学变化如何驱动宿主免疫仍知之甚少。在此，有报道称模拟病理的M-纳米纤维——而非模拟生理的P-纳米纤维——作为一种防御机制，通过操纵免疫反应来帮助恢复组织稳态。体内和体外的定量多组学研究表明，与P-纳米纤维相比，M-纳米纤维通过上调M2巨噬细胞极化和下游免疫信号，显著抑制炎症并促进组织再生。分子分析和理论模拟表明，M-手性对细胞结合表现出更高的立体亲和力，这会诱导更高的细胞收缩应力并激活机械敏感离子通道PIEZOl以引导钙离子内流。反过来，钙离子内流会使信号转导和转录激活因子（STAT）的核转位发生偏向，从而促进M2极化。这些发现强调了疾病的结构机制，为使用仿生功能材料进行免疫治疗提供了设计依据。
