Abstract
Mechanoimmunology is the study of how immune cells sense, respond, adapt, function, and develop in their changing mechanical environment. It is an emerging field compared to that of the mechanobiology of tissue cells. In this talk, I will describe an outside-in/inside-out signaling loop for T-cell receptor mechanotransduction, which is induced by negative selecting ligands in the thymus. This work provides an example immunoreceptor that functions as a mechanosensor.

Bio
Cheng Zhu is a Regents Professor of Biomedical Engineering, Mechanical Engineering, and Physics and holds the J. Erskine Love Endowed Chair in Engineering at the Georgia Institute of Technology and Emory University. His PhD and postdoctoral training with Richard Skalak at Columbia University and University of California, San Diego was on the mathematical modeling of cell locomotion and cell adhesion. But he has also become a self-taught experimentalist since 1990 after he built his own lab at Georgia Tech. A resulting strength of Zhu’s work is integration of theory and experiment. He pioneered the analysis of interactions at the junctional interface between molecules anchored to two apposing surfaces by inventing the required experiments with custom-design instruments and/or by developing the needed mathematical models (Refs. 1-4 below).

Armed by these powerful tools, the Zhu lab characterized the biophysical regulations of 2D binding (Refs. 5-8 below) and showed their biological relevance. In particular, the Zhu lab has shown that in situ measures of TCR–pMHC and TCR–pMHC–CD8 interactions correspond to T-cell effector functionality (Refs. 9-12 below). Zhu also is an internationally recognized leader in molecular biomechanics and mechanobiology. His lab conceptualized and/or demonstrated several types of mechanical regulation of protein unbinding and unfolding (catch bonds, force-history, cyclic mechanical reinforcement, and dynamic catch) in a variety of receptor–ligand systems, including selectins, integrins, platelet glycoprotein Ibα, actin, and T-cell receptors with their respective ligands (Refs. 13-20 below). More recently, the Zhu lab has developed a fluorescence biomembrane force probe (fBFP) to enable concurrent measurements of force-regulated receptor–ligand interaction and intracellular signaling so triggered (cf. Ref. 19 below). Zhu has had a fruitful collaborative relationship with Dr. Michelle Krogsgaard for five years. They have co-authored two papers, one in Eur J Immunol (Refs. 12) and another in J Immunol, and two more collaborative papers are currently in preparation. These collaborations on which the present application builds justify Zhu as a co-I of this grant.