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

皮肤神经元感觉触觉器官的生物物理学及其对机械和化学应力的敏感性

• 批准号: 10320377
• 负责人: Miriam B Goodman
• 金额: $ 69.68万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-15 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10320377
• 关键词: Activities of Daily Living; Address; Affect; Afferent Neurons; Animals; Autoimmune Diseases; Biophysics; Caenorhabditis elegans; Calcium; Chemicals; Diabetes Mellitus; Dissection; Electron Microscopy; Electrophysiology (science); Encapsulated; Engineering; Feedback; Genetic; Genetic Models; Glucose; Health; Human; Image; Invertebrates; Joints; Knowledge; Link; Mechanics; Microtubules; Molecular; Monitor; Morphology; Motion; Movement; Muscle; Nematoda; Neurons; Optics; Organ; Paclitaxel; Patients; Perception; Performance; Peripheral Nervous System Diseases; Quality of life; Research; Signal Transduction; Skin; Spectrin; Stress; Structure; Surface; Tactile; Tissues; Touch sensation; Translating; Traumatic Brain Injury; Visceral; Work; autonomic neuropathy; base; cantilever; chemotherapy; experimental study; mechanical force; mechanical signal; mechanical stimulus; multidisciplinary; programs; simulation; somatosensory; stressor; theories; tool

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.

皮肤、肌肉、关节和内脏器官封装着专门的感觉神经元，可以检测触摸和运动形式的机械线索。执行大多数（如果不是全部）日常生活基本活动的能力取决于来自这些体感、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对于健康至关重要。该研究项目重点关注负责触觉的皮肤-神经元复合组织，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，并转化为产生触觉感知的电信号。这项工作将简单无脊椎动物（秀丽隐杆线虫）的基因解剖与电子显微镜、高性能工具（自感知悬臂）结合起来，用于在反馈控制下传递机械刺激，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，将实验工作与理论和模拟相结合。除了寻求对皮肤-神经元复合材料的机械感觉的全面理解之外，该研究计划还将解决神经元如何弯曲而不断裂的突出问题。基于前期工作，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物来获得触觉的人类。