The Department of Chemical and Biomolecular Engineering welcomes Dr. Steve Abel, Assistant Professor from the University of Tennessee, Knoxville, as a part of the ChBE Spring Seminar series. His seminar, titled “Antigen Recognition at Immune-Cell Surfaces: Probing the Role of Mechanical Forces,” will take place on Thursday, March 29th 2018 from 2:00-3:00pm in Earle 100.
One of the central problems in immunology involves molecular recognition at cell-cell interfaces. T cells and B cells directly engage other cells and use surface receptors to identify molecular signatures of pathogens. Fascinating recent experiments have revealed that mechanical forces regulate processes by which T cells and B cells distinguish between self and foreign ligands, but a unifying theoretical framework is missing. In this work, we develop hybrid computational models that account for key biophysical properties of immune-cell interfaces, including stochastic receptor-ligand binding kinetics, membrane mechanics, and actin-mediated forces on the membrane. We use these models to investigate how mechanical forces modulate the interactions of T cells and B cells with surface-presented antigens. In the case of T cells, we characterize how receptor-ligand bond formation drives dynamic changes in membrane organization and shape, how these changes affect forces experienced by the bonds, and how these forces affect bond lifetimes. In the case of B cells, we show that the bending rigidity of the antigen-presenting membrane influences the affinity at which antigens are internalized through a mechanism involving receptor clustering and membrane invagination. We conclude by discussing our results in the context of antigen discrimination by T cells and B cells, and by highlighting open questions in mechanoimmunology that theoretical approaches can help to address.
Steve Abel received his undergraduate education at Rice University, where he earned a B.S. in Chemical Physics, a B.A. in Mathematics, and a B.A. in Physics. He received a Ph.D. in Chemical Engineering from Stanford University and was a postdoctoral associate in the Department of Chemical Engineering at the Massachusetts Institute of Technology. His graduate research focused on developing theoretical methods to describe the highly correlated motion of molecules in dense liquids. His postdoctoral work applied theory and computation to understand how T cells, the primary orchestrators ofadaptive immunity, identify and respond to pathogens. This work was carried out in close collaboration with experimentalists, with a particular emphasis on understanding how the membrane environment influences signal
transduction in cells. Dr. Abel’s group currently investigates fundamental problems in cell biology and immunology using theoretical and computational methods. They study processes involving signal transduction networks, cell membranes, and the cytoskeleton, with specific interests including antigen recognition and lymphocyte activation, motor-driven intracellular transport, stochasticity in biochemical reaction networks, and soft biological materials.