近年来，泛耐药性病菌的流行成为一个重大的世界卫生安全问题。传统抗生素因为必须参与细菌新陈代谢过程，无法治疗由休眠状态细菌造成的感染，迫切需要发展新型抗菌疗法。以力学破坏细菌细胞膜为目标的膜靶向纳米抗生素，因不参与细菌新陈代谢过程，可以快速杀死休眠状态的病菌，成为解决抗生素耐药性的一个可能的方法。然而，现有对纳米材料抗菌性和人体毒性的理论和实验系统的研究依然不足，基本作用机制尚不清晰，抗生素筛查平台严重匮乏。急需我们建立能够同时检测抗菌性和人体毒性的膜靶向抗生素平台。本项目将借助新型二维纳米材料可塑性和优秀的力学性能，结合理论、计算和实验方法，研究二维纳米材料几何尺寸、形状结构、材料刚度、表面性质、化学结构和基团分布等因素对其与细菌和人体细胞膜发生力学相互作用的过程和机制，揭示二维纳米材料抗菌机制的结构特异性，指导膜靶向纳米抗生素的设计和优化，为纳米抗生素药物的发展和应用奠定力学研究基础。

Recently, the high prevalence of multi-drug resistant strains has become a major public health issue in the world. As conventional antibiotics that target biosynthetic processes are not effective in treating infections caused by persistent bacteria, novel anti-bacterial therapeutics are urgently needed. Membrane-targeting nano-antibiotics that mechanically damage bacterial membrane without targeting biosynthetic processes exhibits fast killing rates on persistent bacteria, which suggests a promising way to solve the problem of antimicrobial resistance. However, the shortage of systematic research on the antimicrobial activity and cytotoxicity of nanomaterials in theory and experiments, the unclear antimicrobial mechanism of nanomaterials and the lack of the platform for antibiotics screening direly need us to build a screening platform for membrane-targeting antibiotics that can test the antimicrobial activity and cytotoxicity simultaneously. In this project, for outstanding structural amenability and excellent mechanical properties of emerging two-dimensional nanomaterials, the interaction between nanomaterials and bacterial or human cell membranes will be investigated by theoretical modeling, atomistic simulations and experimental observation to reveal the roles of size, shape, stiffness, surface character, chemical structure and the functional group on the antimicrobial activity and cytotoxicity of nanomaterials. The structure-activity relationship will be studied to uncover the antimicrobial mechanism of two-dimensional nanomaterials, provide guidelines for the design and optimization of membrane-targeting nano-antibiotics, and lay the foundation for the field of mechanics in the development and application of anti-bacterial nanomedicine.