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: 10633441
• 负责人: Miriam B Goodman
• 金额: $ 22.98万
• 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/10633441
• 关键词: Activities of Daily Living; Address; Affect; Afferent Neurons; Animals; Biophysics; Caenorhabditis elegans; Calcium; Chemicals; Cytoskeleton; Devices; Diabetes Mellitus; Dissection; Electrophysiology (science); Encapsulated; Engineering; Genetic; Genetic Models; Glucose; Health; Human; Image; Invertebrates; Joints; Knowledge; Link; Mechanics; Microfluidics; 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; cantilever; chemotherapy; experimental study; mechanical force; mechanical signal; mechanical stimulus; multidisciplinary; programs; simulation; somatosensory; stressor; theories; tool

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.

项目概要/摘要 皮肤、肌肉、关节和内脏器官封装了专门的感觉神经元，可以检测机械信号 以触​​摸和运动的形式。执行大部分（如果不是全部）日常生活基本活动的能力 依赖于来自这些体感、本体感觉和内脏感觉神经元的信息。因此，一个 更好地了解它们的功能以及对机械和化学应力的敏感性至关重要 为了健康。该研究项目重点关注负责触觉和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，以及 转换成产生触觉感知的电信号。这项工作将基因解剖结合在 简单的无脊椎动物（线虫）与高性能工具（自感应悬臂， 基于微流体的设备）用于传递机械刺激和光学监测组织变形 以及通过电生理学和钙成像进行神经元激活。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。除了寻求一个 全面了解皮肤-神经元复合材料的机械感觉，该研究计划将 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 工作中，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）相关的化学应激源会影响功能和 皮肤-神经元复合物的形态。我们寻求获得的知识与所有动物相关，包括 人类依靠皮肤神经元复合物来获得触觉。