Force Transduction and Tension Sensing at Intercellular Junctions

这项研究项目的目的是确定纳米级的机制，通过细胞感受邻近细胞的张力来调节关键的细胞功能。该程序的智力优势来自于新的、及时的初步发现，明确地证明了：1)一类重要的细胞间黏附蛋白、钙粘附素、感知力可以按比例改变细胞功能；2)这一功能依赖于特定的结合伙伴。这项研究创新地结合了机械探头和活细胞成像技术来研究钙粘蛋白的机械生物学，构成了一个全新的研究领域。这个项目是创新的，因为细胞间机械传感及其对更广泛的细胞力学的影响几乎是一个完全未被探索的研究领域。这项工作将产生广泛的影响，因为钙粘附素对发育、有组织的组织重建和调节组织屏障至关重要。钙粘附素感知力的能力将极大地影响它们调节细胞功能的方式，并扩大机械力对细胞间通讯的广泛影响。由于钙粘附素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数学和工程(游戏)女孩冒险计划和伊利诺伊大学针对少数族裔的暑期研究机会计划(SROP)，在大学预科和本科阶段向妇女和少数族裔伸出援手。我们将在SROP计划的学生的游戏工作坊和研究活动中实施这项提案中的技术。这笔助学金将使我们能够继续在这些外展计划中指导学生。

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.