“Antigen Recognition at Immune-Cell Surfaces: Probing the Role of Mechanical Forces”
Steve Abel, Ph.D.
Assistant Professor
Department of Chemical and Biomolecular Engineering
National Institute for Mathematical and Biological Synthesis
University of Tennessee, Knoxville
Abstract: 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.
Wednesday, July 25th, 2018 at 2:00 pm
Natural Sciences 2, Room 3201
Host: Prof. Elizabeth Read