Dynamic Bio-Mechanical Properties of Ligand-Receptor Bonds

配体-受体键的动态生物力学特性

• 批准号: 1200839
• 负责人: Cetin Cetinkaya
• 金额: $ 36万
• 依托单位: Clarkson University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1200839&HistoricalAwards=false
• 关键词: Dynamic; Bio; Mechanical; Properties; Ligand

The research objective of this award is to characterize, investigate, and understand the dynamic mechanical properties of ligand-receptor adhesion bonds through non-contact, cell-free experiments, with a special emphasis on "catch" bonds. Catch bonds are non-covalent ligand-receptor bonds whose dissociation lifetime counter-intuitively increases with increasing tensile force applied to the bond. In other words, catch bonds become stronger upon elongation. However, wide variations in the published data on the mechanical properties of catch bonds suggest that current experimental approaches are inadequate. Studies conducted under this award hypothesize that compressive force and nonlinearity in stiffness play a role in bond properties, particularly during bond rupture. This hypothesis will be tested by experimental investigations of (i) the effects of external forces not only in tension, but also in compression, on ligand-receptor bonds; (ii) the dynamic adhesion and mechanical stiffness properties of these bonds at various time-scales; (iii) and the level of stiffness nonlinearity in these bonds and its relation to bond lifetime. The long-term goal is to understand the ligand-receptor adhesion mechanisms required for the development of higher-order models. If successful, these studies will add significantly to the field?s understanding of the mechanical properties of ligand-receptor adhesion bonds, including catch bonds. In addition to their potential to increase our fundamental understanding, precise characterization of ligand-receptor bonds may also lead to innovative technologies such as targeted drug delivery, cancer diagnostics, methods for cell sorting, improved tools for computational simulations, and novel classes of sensors and detectors. The project will be conducted by a multi-disciplinary team including faculty from Mechanical Engineering, Chemical and Biomolecular Engineering, and Biology. The educational plan includes course development in the disciplines of the respective Principal Investigators (PIs), participation in the Research Experience for Teachers (RET) program, and incorporation of their results into an ongoing NSF Nanotechnology Undergraduate Education (NUE) project.

该奖项的研究目标是通过非接触、无细胞实验，特别强调“捕获”键，表征、研究和理解配体-受体粘附键的动态机械特性。捕获键是非共价配体-受体键，其解离寿命随着施加到键上的张力的增加而增加，这与直觉相反。 换句话说，捕捉键在伸长时变得更强。 然而，已发表的关于卡扣键机械性能的数据存在很大差异，这表明当前的实验方法是不够的。根据该奖项进行的研究假设，压缩力和刚度非线性在粘合性能中发挥着重要作用，特别是在粘合断裂期间。 这一假设将通过以下实验研究得到检验：(i) 外力不仅对配体-受体键的张力产生影响，而且对压力产生影响； (ii) 这些粘合在不同时间尺度下的动态粘合和机械刚度特性； (iii) 以及这些键的刚度非线性水平及其与键寿命的关系。 长期目标是了解开发高阶模型所需的配体-受体粘附机制。如果成功，这些研究将显着增进该领域对配体-受体粘附键（包括捕获键）机械性能的理解。除了增强我们的基本理解之外，配体-受体键的精确表征还可能带来创新技术，例如靶向药物输送、癌症诊断、细胞分选方法、改进的计算模拟工具以及新型传感器和传感器。探测器。该项目将由一个多学科团队进行，其中包括机械工程、化学和生物分子工程以及生物学的教师。该教育计划包括各自首席研究员 (PI) 学科的课程开发、参与教师研究经验 (RET) 计划以及将其成果纳入正在进行的 NSF 纳米技术本科教育 (NUE) 项目。