Dynamic Bio-Mechanical Properties of Ligand-Receptor Bonds

该奖项的研究目标是通过非接触，无细胞实验来表征，调查和了解配体-受体粘附键的动态力学特性，特别强调“捕获”键。捕获键是非共价配体-受体键，其解离寿命随着施加到键的张力的增加而反直觉地增加。 换句话说，捕捉键在伸长时变得更强。 然而，广泛的变化，在已公布的数据上的机械性能的捕捉债券表明，目前的实验方法是不够的。根据该奖项进行的研究假设，压缩力和刚度的非线性在粘结性能中发挥作用，特别是在粘结断裂期间。 这一假设将通过以下实验研究进行检验：（i）外力不仅在拉伸中，而且在压缩中对配体-受体键的影响;（ii）这些键在不同时间尺度下的动态粘附力和机械刚度特性;（iii）这些键的刚度非线性水平及其与键寿命的关系。 长期目标是了解高阶模型开发所需的配体-受体粘附机制。如果成功，这些研究将大大增加该领域？对配体-受体粘附键（包括捕获键）的机械性质的理解。除了有可能增加我们的基本理解外，配体-受体键的精确表征还可能导致创新技术，如靶向药物递送，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检测器。该项目将由一个多学科团队进行，包括机械工程，化学和生物分子工程以及生物学的教师。教育计划包括在各自的主要研究者（PI）的学科课程开发，在教师（RET）计划的研究经验的参与，并将其结果纳入正在进行的NSF纳米技术本科教育（NUE）项目。

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.