响应外界刺激是生物体的一种重要能力，机械敏感性离子通道作为一种可以将机械刺激转换为电信号或生化信号的分子开关，在生理功能和病理变化中的重要调节作用越来越受到人们的重视。该项目以机械敏感性离子通道MscL为研究模型，应用定点突变，半胱氨酸扫描，色氨酸扫描，电荷排斥，FRET，荧光释放，化学标记，同源嵌合体，多聚体基因改造等研究方法，结合膜片钳单通道记录，蛋白质重组脂质体技术，以及荧光分析手段，阐明MscL开放过程中跨膜区域，N-端，C-端，Loop等关键区域之间的"区域-区域"相互关系以及构象变化，以及MscL功能区域和膜脂质的"区域-脂质"相互作用，从整体水平明确机械敏感性离子通道结构和功能的关系，定位关键功能位点，揭示MscL的开放机制并建立通道门控模型。进而根据结构新模型修饰MscL的机械敏感性，物质通透性，优化和改造通道功能，为MscL在生物医药和纳米生物感受器方面的应用奠定基础。

Mechanosensation is the ability to detect the mechanical force and is essential to the life. Mechanosensitive ion channel, as a molecular switch to transfer the mechanical stimuli into electrial or chemical signals, plays the important role in the mechanosensation. In the project, we use mechanosensitive channel MscL as a research model, utilizing site-specific mutagenesis, SCAN, SWAN, electrostatic repulation, FRET, Fluorescene release, chemical labeling, chimera, poly-DNA modification methods, combining patch clamp, proteoliposome reconstitution, fluorescense analysis, to determine the interactions and the conformation changes occurred upon gating between the functional domains of MscL, such as transmembrane domain TM1 and TM2, N-terminal, C-terminal, Loop domain, etc., and also to demonstrate the interactions between the funtional domains and membrane lipids. The study will reveal the gating mechanism of MscL, locate the key amano acid positions, present the new model of how MscL sense and respond to the stimuli. According to this model, modification and optimization of the function of MscL can be done, which establish a good foundation to utilze the MscL in biomedcine and nanobiosensor.