Mechanical forces regulate processes ranging from cell division to cell migration, indicating that physical forces are critical to most, if not all, living systems. The aim of this CAREER project is to revolutionize the study of mechanotransduction by developing new methods to map and manipulate molecular forces in living cells. Specifically, the research project will focus on studying integrin-based focal adhesions as a test-bed model for mechanotransduction. The investigators will employ a recently developed fluorescence-based force sensor to image the mechanical tension exerted across integrin receptors in real-time and in living cells. This experimental platform will be used to dissect the earliest steps of chemical recognition and integrin activation, thus probing the existence of integrin-ligand bonds that strengthen under mechanical tension ("catch" bonds) in nascent adhesions of spreading cells. These experiments will determine how mechanical forces are transmitted to focal adhesions that ultimately influence cellular functions. The proposed program will yield a quantitative description of mechanoregulatory processes, thus providing new tools to broadly improve our understanding of mechanotransduction.
Broader Impact The interface between physical and biological sciences is a field rich with questions that are expected to excite many future generations of scientists. Therefore, the educational goal of this program is to foster the pipeline of highly trained scientists that will fulfill our nation's needs in this area. Correspondingly, the PI will develop a dedicated biophysics course and modern laboratory experiments that will expand multidisciplinary education. To reach out to the general public and entice the coming generation of students, the CAREER project will develop entertaining, informative, and interactive animations illustrating fundamental concepts pertaining to mechanobiology. Through targeted dissemination to high school teachers, YouTube, the CancerQuest educational website (with over 140,000 Facebook fans), and iTunes U the PI will share these animations with audiences ranging from the lay-person to pre-college students. By leveraging the GK-12 and HHMI grant programs already in place at Emory University, and by initiating an outreach program to Atlanta metro public high schools, the project will attract young people to the physical and biological sciences. This program represents an integrated effort that will leverage existing resources to raise the scientific literacy of the general public and attract students to the fertile multidisciplinary research programs that span the areas of cell biology and biophysical chemistry.
This grant is funded jointly by the Cellular Dynamics Program in the Division of Molecular and Cellular Biosciences and the Chemistry of Life Sciences program in the Division of Chemistry.
