Modeling the mechanisms for formation of LAT condensates

Recognition of foreign peptides by T-cells is vital for cell-mediated immunity in response to infection with viruses and bacteria. T-cells achieve robust recognition of foreign peptides through a sequence of biochemical, non-equilibrium kinetic proofreading steps involving the T-cell receptor and other proteins. One of the steps is the formation of a protein condensate around the T-cell receptor involving the protein Linker for the Activation of T-cells (LAT). Several experimental studies have investigated the formation of LAT condensates using reconstitution experiments on supported lipid bilayers. These experiments show (1) a long lag time until condensation and (2) near-stationary patterns after condensation with non-circular boundaries and widely varying morphologies across different realizations of the experiment. To understand the long lag time, we use the Smoluchowski aggregation model to show that a slow binding rate can yield a characteristic onset time far exceeding the diffusion time scale. To understand the different patterns observed in reconstitution experiments, we propose a field-theoretic model that couples the dynamics of LAT to the bond density. This model captures the morphology and diversity of patterns observed in reconstitution experiments. Specifically, the slowing down of diffusion upon condensation leads to stationary, non-circular geometries, and varying the initial LAT density and free energy parameters reproduces the different observed morphologies.