Modeling the Coalescence Kinetics of Cell Surface Receptor Clusters

Abstract

Cells in a multicellular organism must be ready to respond to a variety of extracellular signals such as ligands on the surface of cells or parasites. To understand these signaling mechanisms, many current experiments investigate transmembrane signaling of immunoreceptors on B cells, T cells, or mast cells, initiated by binding to specific monovalent ligands in fluid membranes. In mast cells, receptor clusters initially form at cellular protrusions through diffusion mediated trapping, undergo primarily diffusive motion with a partial directed element as well, and eventually coalesce at a finite rate to form a large central receptor patch termed synapse (Spendier et al. 2010. Biophys. J. 99:388–397). We are currently developing a coalescence theory to investigate the kinetics of receptor cluster coalescence in detail, which is important in understanding the mechanism and dynamics of cellular signaling. Our coalescence theory is split into trapping considerations, which generalize Smoluchowski's well known theory for arbitrary melding probability, and a feedback idea. Trapping considerations were developed with a unified approach constructed earlier for excitons (Kenkre and Reineker. 1982. Exciton Dynamics in Molecular Crystals and Aggregates. Springer, Berlin) to compute the particle survival probability for any dimension and motion due to a closed or open trapping surface. To build a coalescence theory, we use our trapping prescription to compute the rate at which particles disappear and solve for the time dependent trap radius through a self-consistent approach. We find that our coalescence theory for a finite melding probability is in good agreement with simulations.