The biophysics of skin-neuron sensory tactile organs and their sensitivity to mechanical and chemical stress

皮肤、肌肉、关节和内部器官包裹着专门的感觉神经元，这些神经元以触摸和运动的形式检测机械信号。日常生活中大部分（如果不是全部）基本活动的执行能力都依赖于来自这些体感、本体感受和内脏感觉神经元的信息。因此，更好地了解它们的功能和对机械和化学应力的敏感性对健康至关重要。本研究项目聚焦于负责触觉的皮肤神经元复合组织，并试图破译机械力如何从皮肤表面转化为嵌入的感觉神经元，并转化为产生触觉感知的电信号。这项工作将简单的无脊椎动物（秀丽隐杆线虫）的遗传解剖与电子显微镜、高性能工具（自传感悬臂）结合起来，在反馈控制下提供机械刺激，并通过电生理学和钙成像光学监测组织变形和神经元激活。研究团队包括生物学家、工程师和物理学家，并将实验工作与理论和模拟相结合。除了寻求对皮肤神经元复合材料机械感觉的全面理解外，该研究项目还将解决神经元如何弯曲而不断裂的突出问题。在前期工作的基础上，我们还计划利用我们的触觉知识及其分子基础来研究与糖尿病（葡萄糖）和化疗（紫杉醇）相关的化学应激源如何影响皮肤神经元复合物的功能和形态。我们寻求获得的知识与所有动物相关，包括依赖皮肤神经元复合材料产生触觉的人类。

Skin, muscle, joints, and internal organs encapsulate specialized sensory neurons that detect mechanical cues in the form of touch and movement. The ability to perform most, if not all of the essential activities of daily living depends on information from these somatosensory, proprioceptive, and visceral sensory neurons. Thus, a better understanding of their function and sensitivity to mechanical and chemical stress is of vital importance for health. This research program focuses on the skin-neuron composite tissues responsible for touch and seeks to decipher how mechanical force is translated from the skin surface to embedded sensory neurons and converted into electrical signals that give rise to tactile perceptions. The work combines genetic dissection in a simple invertebrate (C. elegans nematodes) with electron microscopy, high-performance tools (self-sensing cantilevers) for delivering mechanical stimuli under feedback control and for optically monitoring tissue deformation and neuronal activation with electrophysiology and calcium imaging. The research team includes biologists, engineers and physicists and integrates experimental work with theory and simulation. In addition to seeking a comprehensive understanding of mechanosensation by skin-neuron composites, the research program will also address the outstanding question of how neurons bend without breaking. Based on preliminary work, we also plan to leverage our knowledge of touch sensation and its molecular basis to investigate how chemical stressors linked to diabetes (glucose) and chemotherapy (paclitaxel) affect the function and morphology of skin-neuron composites. The knowledge we seek to acquire is relevant to all animals, including humans that rely on skin-neuron composites for touch sensation.