基于暗场光谱成像的单分子力谱分析及其在单细胞水平上机械力信号传导中的应用

Mechanical force signaling between cells and extracellular environmental has been generally recognized as the biological foundation of different important physiological processes including the senses of touch, hear, pressure, pain and balance. The disorders in the feelings of mechanical force by cells in these processes are closely related to many clinical diseases, for example, hearing loss and muscular dystrophy. Recent investigations have also revealed that mechanical force plays significant regulatory roles in many fundamental biological functions, such as cell adhesion, migration, proliferation and differentiation, which are involved in the physiological processes including tissue development, cancer metastasis, wound healing and so on. Therefore, investigating mechanical force transduction at single-cell level has great significance for biological and physiological studies. By taking advantage of the superior properties of plasmonic nanoparticles and dark-field spectral imaging, we designed a novel dark-field single-molecule force spectroscopy. With this technique, the distribution and fluctuation of mechanical signals at single-cell level during different biological processes including cell migration, cell proliferation and cell differentiation be investigated. The correlation between cell functions and mechanical signal regulation can also be revealed. These investigations are promising to provide new way for quantitative analysis of mechanical signal transduction with high spatial and temporal resolution, which has profound impact for the studies in the field of biomechanics, mechanical signal transduction mechanisms, mechanical signal disorder induced diseases and dynamics of cellular cytoskeleton.

细胞对环境中机械力信号的感知是触觉，听觉，压觉、痛觉以及平衡觉等在内的许多重要生理过程的生物学基础，这一感受过程的紊乱也与很多临床疾病密切相关。近年来的研究表明，机械力信号在许多细胞生物学过程中也起到关键作用。因此，在细胞层面上研究机械力信号及其传导机制具有重要的生物学与生理学意义。本项目计划综合利用等离激元纳米粒子独有的优良性能和暗场光谱成像技术的优势，发展新型高灵敏暗场单分子力谱分析技术。利用该技术考察细胞迁移、分裂与分化等一系列细胞生命活动中的机械力信号的分布差异与变化规律，探索机械力信号变化与细胞活动的动态关联，并研究机该异常变化对细胞正常生物学功能的影响。本研究项目的开展有望为细胞生物学中的机械力相关过程提供高分辨率的定量分析手段，从而为细胞力学，机械力信号的传导机制，机械力信号紊乱相关疾病的发病机理以及细胞骨架动力学等基础与应用研究产生重要的影响。

细胞对环境中机械力信号的感知是触觉，听觉，压觉、痛觉以及平衡觉等在内的许多重要生理过程的生物学基础，这一感受过程的紊乱也与很多临床疾病密切相关。近年来的研究表明，机械力信号在许多细胞生物学过程中也起到关键作用。因此，在细胞层面上研究机械力信号及其传导机制具有重要的生物学与生理学意义。本项目利用等离激元纳米粒子独有的优良性能和暗场光谱成像技术的优势，发展了新型高灵敏暗场单分子力谱分析技术。利用该方法，实现了同时测量贴壁细胞表面多个力学信号受体分子感知机械力信号的动态变化，并对外界刺激诱导机械力信号传导的过程进行了实时监测。这一方法的开发和应用研究，为细胞生物力学信号传导的调节过程及相关机制的研究提供了新的分析工具。