Dynamic Bio-Mechanical Properties of Ligand-Receptor Bonds

该奖项的研究目标是通过非接触、无细胞的实验来表征、调查和了解配体-受体粘附键的动态机械性质，特别强调“捕捉”键。CATCH键是一种非共价配体-受体键，其解离寿命随施加在键上的张力的增加而反直观地增加。换句话说，渔获物的结合在伸长后变得更牢固。然而，已发表的关于捕获键的机械性能的数据差异很大，这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，压缩力和硬度的非线性对键性能起作用，特别是在键断裂期间。这一假设将通过以下实验研究来验证：(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上的动态粘附性和机械刚性性质；(Iii)这些键中的刚性非线性程度及其与键寿命的关系。长期目标是了解发展高阶模型所需的配体-受体黏附机制。如果成功，这些研究将大大增加S领域对包括捕获键在内的配体-受体粘附键的力学性质的了解。除了有可能增加我们对配体-受体键的基本了解外，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检测器。该项目将由一个多学科团队进行，其中包括来自机械工程、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首席研究人员(PI)的学科中开发课程，参与教师研究经验(RET)计划，并将他们的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.