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

皮肤、肌肉、关节和内脏包裹着专门的感觉神经元，这些神经元可以检测触摸和运动形式的机械线索。如果不是全部，执行日常生活的大部分基本活动的能力依赖于来自这些躯体感觉、本体感觉和内脏感觉神经元的信息。因此，更好地了解它们的功能以及对机械和化学应激的敏感性对健康至关重要。这项研究计划专注于负责触摸的皮肤-神经元复合组织，并试图破译机械力如何从皮肤表面转移到嵌入的感觉神经元，并转化为产生触觉的电信号。这项工作将简单无脊椎动物(线虫)的基因解剖与电子显微镜、用于在反馈控制下传递机械刺激的高性能工具(自感知悬臂)以及通过电生理学和钙成像对组织变形和神经元激活进行光学监测相结合。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。除了寻求全面了解皮肤-神经元复合材料的机械感觉外，该研究计划还将解决神经元如何弯曲而不断裂的悬而未决的问题。在前期工作的基础上，我们还计划利用我们对触摸感觉及其分子基础的知识，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-神经元复合材料的功能和形态。我们寻求获得的知识与所有动物相关，包括依赖皮肤-神经元复合体进行触摸感觉的人类。

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.