细胞对于环境中机械力信号的感受是许多重要生理过程的生物学基础，其关键过程是将机械力刺激转化为细胞内电或者化学信号，即机械力信号转导。在过去的三十年中，人们利用多种模式生物对这一过程进行了系统的研究，但是在细胞生物学水平上了解其结构和功能基础的工作仍需要进一步深入。在前期工作中，我们以果蝇力敏感细胞为模型发现了负责力信号转导的特化细胞器（“力感受器” ），证明了它的核心是由力敏感通道NompC和微管骨架组成的复合物，并提出了“链式模型”来描述力信号转导的机制。本项目将应用电子断层成像技术和力信号记录等新技术并结合分子细胞生物学手段对力感受器的结构和功能开展深入研究并进一步检验和完善“链式模型”。本项目的目标是建立力感受器的结构力学模型，系统地了解力感受器在机械力信号转导过程中的运作机制及其关键分子NompC的作用，这一研究将为理解机械力信号转导的原理打下坚实的细胞生物学基础。

The sense of mechanical stimuli (e.g. force or deformation) in the environment underlies several important physiological processes, for example the perception of touch, sound, acceleration and flow. The process that converts the environmental mechanical stimuli into intracellular signals is termed as mechanotransduction. In the past 30 years, despite intensive efforts made in various model organisms, the cell biological mechanisms of mechanotransduction still remain elusive. In our previous work, we identified the mechanoreceptive organelle in fly mechanosensory cells and found that the NompC-microtubule complex is the core of this organelle. Based on these findings, we hypothesized a “linkage model” to account for the mechanism of fly mechanotransduction. In the present proposal, we will further dissect the molecular, structural and mechanical basis of the mechanoreceptive organelle and test the “linkage model”. First, we will reconstruct the three-dimensional structure of the mechanoreceptive organelle using electron tomography (ET) technique. Based on the ET results, we will measure the geometry of all structural elements in the organelle and build the wild-type structure model. Second, we will study the structures of the mechanoreceptive organelles in various NompC mutants to understand the structural roles of NompC and its ankyrin-repeats domain. Third, we will measure the mechanical properties of the organelle using the MEMS-based force measurement technique. In combination with the structural studies, we would be able to build the mechanics-structure model of the organelle. Fourth, we will perform the mechanical measurements on the organelle of the NompC mutants to understand the mechanical roles of NompC. In summary, we aim to understand the molecular, structural and mechanical basis of the mechanoreceptive organelle in fly mechanotransduction and the contributions of a key molecule, NompC. This study will establish a solid basis for understanding the principle of mechanotransduction, as well as the relevance of mechanotransduction in clinical diseases.