Force Transduction and Tension Sensing at Intercellular Junctions

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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.