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

项目概要/摘要 皮肤、肌肉、关节和内脏都包裹着专门的感觉神经元，这些神经元可以检测到机械信号 以触摸和运动的形式。完成大部分日常生活基本活动的能力，如果不是全部的话 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力的敏感性是至关重要的 为了健康这项研究计划的重点是皮肤神经元复合组织负责触摸， 试图破译机械力是如何从皮肤表面传递到嵌入的感觉神经元的， 转换成电信号，产生触觉感知。这项工作结合了基因解剖， 简单无脊椎动物（C.线虫）与高性能工具（自感知杠杆， 用于传递机械刺激和用于光学监测组织变形 和神经元激活与电生理学和钙成像。研究小组包括生物学家， 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A 通过皮肤-神经元复合材料对机械感觉的全面理解，研究计划将 继续解决神经元如何弯曲而不断裂的悬而未决的问题。根据初步 工作，我们还计划利用我们对触觉及其分子基础的知识来研究如何 与糖尿病（葡萄糖）和化疗（紫杉醇）相关的化学应激源影响功能， 皮肤-神经元复合物的形态学。我们寻求获得的知识与所有动物有关，包括 依靠皮肤神经复合物来获得触觉的人类。

Project Summary/Abstract 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 depend 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 high-performance tools (self-sensing cantilevers, microfluidics-based devices) for delivering mechanical stimuli 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 continue to 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.