Force Clamp Systems for Evaluation of Mechanotransduction

用于评估机械传导的力夹系统

• 批准号: 7465346
• 负责人: Beth L Pruitt
• 金额: $ 30.06万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7465346
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Affect; Agar; Animals; Atomic Force Microscopy; Behavior; Behavioral; Biochemical; Biocompatible Materials; Biological; Biological Assay; Biological Models; Biomechanics; Caenorhabditis elegans; Cell membrane; Cell physiology; Cells; Communities; Complex; Coupling; Custom; Cytoskeleton; Data; Development; Devices; Diabetes Mellitus; Disease; Drug Design; Electronics; Electrophysiology (science); Esthesia; Evaluation; Exhibits; Extracellular Matrix; Feedback; Financial compensation; Fire - disasters; Floor; Freedom; Frequencies; Gated Ion Channel; Generations; Glass; Gold; Hair Cells; Health Care Costs; Image; In Vitro; Inherited; Ion Channel; Ions; Kinetics; Letters; Malignant Neoplasms; Measurement; Measures; Mechanics; Mediating; Methods; Modeling; Molecular; Mutation; Nematoda; Neurons; Neuropathy; Noise; Output; Pain; Pattern; Performance; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Physical Stimulation; Physiological; Physiology; Play; Process; Property; Proprioception; Public Health; Quantitative Evaluations; Ramp; Range; Rate; Reaction Time; Relaxation; Research; Research Personnel; Role; Scanning; Sensory; Shapes; Signal Transduction; Silicon; Skin; Spinal Ganglia; Standards of Weights and Measures; Stimulus; Structure; Surface; System; Techniques; Technology; Temperature; Testing; Therapeutic; Time; Tissues; Touch sensation; Travel; Variant; Vertebrates; Wood material; Work; base; cantilever; cost; design; desire; in vivo; innovation; insight; instrumentation; laser tweezer; microsystems; mutant; nano; novel; optical imaging; patch clamp; programs; prototype; receptor; reconstitution; research study; response; sensor; sensory neuropathy; somatosensory; tool; viscoelasticity; voltage

DESCRIPTION (provided by applicant): This work proposes a fully integrated approach to the study of mechano-electrical transduction in the sense of touch and focuses on the development of a novel microsystems-based tool-namely, a force clamp that uses appropriately-scaled piezeoresistive cantilevers as direct force sensors (PR force clamp). The proposal includes work to fully characterize the capabilities of a first-generation device, to design and build a second- generation device capable of operating at higher bandwidth, and to use these devices to analyze and model the biomechanics offeree transfer and mechano-electrical transduction by a model mechahoreceptor cell, the touch receptor neurons that innervate the body wall of the nematode Caenorhabditis elegans. C. elegans is an excellent biological platform for developing the proposed tools, which are likely to find application in the study of mechano-electrical transduction in other mechanosensory cells including vertebrate hair cells and dorsal root ganglion. A set of only six touch receptor neurons is responsible for behavioral responses to touch in C. elegans (compared to tens of thousands in vertebrates) and such responses are initiated by activation of the MEC-4 channel complex by forces applied to the body wall. Prototype force clamp systems use PR force clamps and piezoelectric actuators with programmable controllers to apply calibrated nano- to micro-Newton point load profiles with > 1kHz bandwidth. A critical and innovative aspect of this work is the integration of the PR force clamp with patch-clamp electrophysiology for synchronous force-displacement- physiological recordings. This technology will enable the first direct measurement of dynamic changes in tissue stiffness that may occur during mechano-electrical transduction and give rise to adaptation. Relevance to public health. The sense of touch can be degraded by both inherited and acquired disease, including AIDS and diabetes, as well as by chemotherapeutic drugs. Complications from such peripheral sensory neuropathies are estimated to cost more than $4 billion annual in health care costs. Despite this, the sense of touch and its degradation in disease remain poorly understood. The research tools developed in the course of this work have the potential to significantly advance our understanding.

描述（由申请人提供）：这项工作提出了一种完全集成的方法来研究触摸的机械 - 电导转导的研究，并着重于开发基于新型微型系统的工具，即一种力夹，一种使用适当缩放的Piezeoresisisissistive悬臂作为直接力传感器（PR力夹具）（PR力夹具）。 The proposal includes work to fully characterize the capabilities of a first-generation device, to design and build a second- generation device capable of operating at higher bandwidth, and to use these devices to analyze and model the biomechanics offeree transfer and mechano-electrical transduction by a model mechahoreceptor cell, the touch receptor neurons that innervate the body wall of the nematode Caenorhabditis elegans.秀丽隐杆线虫是开发提出的工具的绝佳生物学平台，该工具很可能在研究机械 - 电导型转导中的应用中使用，包括脊椎动物毛细胞和背侧根神经节。一组仅六个触摸受体神经元负责秀丽隐杆线虫中触摸的行为反应（与数以万计的脊椎动物相比），这种反应是通过应用于人体壁的力来激活MEC-4通道复合物的。原型强制夹具系统使用PR力夹和压电执行器与可编程控制器使用具有> 1kHz带宽的校准纳米 - 纳米 - 纳米 - 纳米 - 纳米。这项工作的关键和创新方面是将PR力夹与贴片夹电生理学的整合，用于同步力 - 置换生理记录。该技术将首先直接测量机械电气传输过程中可能发生的组织刚度的动态变化，并引起适应性。与公共卫生有关。遗传和获得性疾病（包括艾滋病和糖尿病）以及化学治疗药物都可以降解触觉。这种外周感官神经病的并发症估计每年的医疗费用耗资超过40亿美元。尽管如此，触感及其在疾病中的降解仍然知之甚少。在这项工作过程中开发的研究工具有可能大大提高我们的理解。