Multiaxial Single-Cell Biomechanics for Mechanotransduction

用于力传导的多轴单细胞生物力学

基本信息

批准号：
7365278
负责人：
SEAN S KOHLES
金额：
$ 21.91万
依托单位：
PORTLAND STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7365278
关键词：
Academic Research Enhancement Awards Accounting Adult Affect Age American Apoptosis Arthritis Award Behavior Biocompatible Materials Biological Biology Biomechanics Biomedical Engineering Biosensor Bos taurus Calcified Cartilage Cattle Cell division Cell physiology Cells Cellular Structures Characteristics Chemistry Chondrocytes Chronic Condition Consensus Custom Degenerative polyarthritis Depth Development Devices Engineering Environment Etiology Extracellular Matrix Facility Construction Funding Category Fatigue Focal Adhesions Foundations Future Goals Grant Harvest Health Housing Human Image Individual Institution Integrins Joints Knowledge Laboratories Lasers Left Life Liquid substance Mathematics Measures Mechanical Stress Mechanics Medicine Microfluidics Molecular Molecular Structure Monitor Optics Outcome Pathogenesis Pathologic Phenotype Physics Process Production Property Regulation Research Resolution Science Signal Transduction Standards of Weights and Measures Stress Structure Students Surface System Technology Testing Therapeutic Tissue Engineering Tissues Today Universities Validation Velocimetries Weight-Bearing state Work articular cartilage base cartilage cell design disability engineering design experience extracellular fluid flow innovation insight laser tweezer particle programs receptor response theories tool transmission process university student

项目摘要

DESCRIPTION (provided by applicant): The development, remodeling, and pathogenesis of many tissues depend in part on mechanical signals. The foundation of mechanotransduction which transforms the mechanical environment experienced by articular cartilage into a biomolecular response will initially be explored through single chondrocyte manipulation. Healthy chondrocytes experience hydrostatic, compressive, tensile, and shear forces that maintain the phenotype and production of neocartilaginous tissue. Abnormal mechanical forces due to single cycle or fatigue loading, have been shown to alter chondrocyte behavior, resulting in pathological matrix synthesis, increased catabolic activity (degradation), and ultimately osteoarthritis (apoptosis). Studies of the biomechanics of single cells originating from the specific cartilage zones are critical for deciphering the transmission of heterogeneous tissue-level forces to the molecular machinery within the cell. A more complete knowledge of individual cellular biomechanics will prioritize the biomechanical factors most critical to stimulating regenerative processes. As there is no consensus as to the mechanical signals that are optimally effective in modulating cell function, much is left to be studied. We recently developed an integrated /micro- particle image velocimetry/optical tweezers (5PIVOT) system toward this goal. This device was designed as a unique tool intended to study cellular mechanics and facilitate the characterization of mechanobiology. The laser-based technologies have been custom-integrated to physically hold cellular or molecular structures concomitant with monitoring fluid and optical force-induced deformations of the structure. The objective of this project is to establish the feasibility of applying an 5PIVOT system for single chondrocyte biomechanics as a precursor to mechanotransduction. This effort will support the Academic Research Enhancement Award (AREA) Program as directed by the following specific aims: 1) to optimize the integration of two optical systems, not previously used in concert, for measuring multiaxial biomechanical properties of single living cells; 2) to apply a sequence of single and multiple axis stresses to individual chondrocytes while measuring the resulting strain response. Successful outcomes from this AREA can then be used to explore the environment most effective in inducing mechanotransduction. Completion of these studies should provide significant insight into the mechanical response of chondrocytes, contribute to the understanding of pathologic cell states and therapeutic approaches for load-bearing tissues, and guide the design of engineered biomaterials which control cellular function

描述（由申请人提供）：许多组织的发育，重塑和发病机理部分取决于机械信号。机械转导的基础最初将通过单个软骨细胞操作来探索关节软骨所经历的机械环境转化为生物分子反应的机械环境。健康的软骨细胞会经历静水，压缩，拉伸力和剪切力，可维持新脂肪组织的表型和产生。由于单个周期或疲劳负荷引起的异常机械力，已显示会改变软骨细胞行为，从而导致病理基质合成，分解代谢活性增加（降解）和最终导致骨关节炎（凋亡）。对起源于特定软骨区域的单细胞的生物力学的研究对于将异质组织水平力向细胞内的分子机械传播的传播至关重要。对单个细胞生物力学的更完整的了解将优先考虑刺激再生过程至关重要的生物力学因素。由于对于在调节细胞功能方面具有最佳有效的机械信号尚无共识，因此仍有很多研究。我们最近将一个集成 /微粒图像速度计 /光镊（5Pivot）系统针对此目标开发了。该设备被设计为一种独特的工具，旨在研究细胞力学并促进机械生物学的表征。基于激光的技术已被定制，以便在物理上保持细胞或分子结构与监测流体和光学力诱导的结构变形相关。该项目的目的是建立将5个远程系统应用于单软骨细胞生物力学的可行性，作为机械转移的先驱。这项工作将按照以下特定目的为学术研究增强奖（区域）计划（区域）计划：1）优化两个以前在协同中不使用的光学系统的集成，用于测量单个活细胞的多轴生物力学特性； 2）在测量所得的应变反应的同时，将一系列单轴和多个轴应力应用于单个软骨细胞。然后，可以使用该领域的成功结果来探索最有效诱导机械转移的环境。这些研究的完成应为软骨细胞的机械反应提供重大洞察力，有助于理解病理细胞态和负载组织的治疗方法，并指导控制细胞功能的工程生物材料的设计