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.

项目摘要/摘要 皮肤、肌肉、关节和内脏包裹着专门的感觉神经元，可以检测机械信号。 以触摸和移动的形式。能够进行日常生活中的大部分基本活动，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，一个 更好地了解它们的功能和对机械和化学应力的敏感性是至关重要的 为了健康。这项研究的重点是皮肤-神经元复合组织，负责触摸和 试图破译机械力是如何从皮肤表面转移到嵌入的感觉神经元和 转换成电信号，产生触觉感知。这项工作将基因解剖结合在一起 简单的无脊椎动物(线虫)和高性能的工具(自我感应悬臂， 基于微流体的装置)，用于传递机械刺激和用于光学监视组织变形 以及电生理和钙成像的神经元激活。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。除了寻求一种 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。基于初步的 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 与糖尿病(葡萄糖)和化疗(紫杉醇)有关的化学应激物影响功能和 皮肤-神经元复合体的形态。我们寻求获得的知识与所有动物相关，包括 依靠皮肤-神经元复合体获得触觉的人类。