Force Transduction and Tension Sensing at Intercellular Junctions

该研究项目的目的是确定纳米机制，细胞通过这种机制感知邻近细胞的张力，以调节关键的细胞功能。 该计划的知识价值来自新颖，及时的初步发现，明确证明i）细胞间粘附蛋白，钙粘蛋白，一个基本类别的感觉力成比例地改变细胞功能，ii）这种功能取决于特定的结合伴侣。本研究采用机械探针和活细胞成像的创新组合，研究钙粘蛋白的机械生物学，构成了一个全新的研究领域。 这项计划是创新的，因为细胞间的机械传感及其对更广泛的细胞力学的影响是一个几乎完全未开发的研究领域。这项工作将产生广泛的影响，因为钙粘蛋白是至关重要的发展，有组织的组织重塑，并调节组织屏障。钙粘蛋白感知力的能力将极大地影响它们如何调节细胞功能，并扩大机械力对细胞间通讯的广泛影响。 由于钙粘蛋白对人类健康和普通生物学的重要性，这项工作将影响从基础生物学到生物工程和临床的各个领域。该计划的教育影响包括通过女孩数学和工程冒险（游戏）计划以及伊利诺伊大学少数民族夏季研究机会计划（SROP）在大学预科和本科阶段与妇女和少数民族进行外联。 我们将在游戏研讨会和研究活动中为SROP计划的学生实施本提案中的技术。 这笔赠款将使我们能够继续指导学生在这些推广计划。

The objective of this research project is to identify nanoscale mechanisms by which cells sense tension in neighboring cells to regulate critical cell functions. The intellectual merit of this program derives from novel, timely preliminary findings demonstrating definitively i) that an essential class of intercellular adhesion proteins, cadherins, sense force to proportionally alter cell functions and ii) that this function depends on specific binding partners. This research uses an innovative combination of mechanical probes and live cell imaging, to investigate cadherin mechanobiology, and constitutes an entirely new research area. This program is innovative because intercellular mechanosensing and its impact on the broader cell mechanics is an almost entirely unexplored research area.This work will have broad impact because cadherins are critical for development, organized tissue remodeling, and regulating tissue barriers. Cadherins capacity to sense force would dramatically impact how they regulate cell functions, and expand the broad impact of mechanical force on cell-cell communication. Because of cadherins importance for human health and general biology, this work will impact fields ranging from basic biology to bioengineering and the clinic. The educational impact of this program includes outreach to women and minorities at pre-college and undergraduate levels through the Girls Adventures in Mathematics and Engineering (GAMES)program and with the Summer Research Opportunity Program for minorities (SROP) at the University of Illinois. We will implement technologies in this proposal in GAMES workshops and research activities for students in the SROP program. This grant will enable us to continue mentoring students in these outreach programs.