Supplementary Figures from A spatio-temporal model reveals self-limiting Fc<i>ɛ</i>RI cross-linking by multivalent antigens release_pqhq67yg3vgoxcwivgnjdpfqxa

by Md Shahinuzzaman, Jawahar Khetan, Dipak Barua

Published by Figshare.



Aggregation of cell surface receptor proteins by multivalent antigens is an essential early step for immune cell signalling. A number of experimental and modelling studies in the past have investigated multivalent ligand-mediated aggregation of IgE receptors (Fc<i>ɛ</i>RI) in the plasma membrane of mast cells. However, understanding of the mechanisms of Fc<i>ɛ</i>RI aggregation remains incomplete. Experimental reports indicate that Fc<i>ɛ</i>RI forms relatively small and finite-sized clusters when stimulated by a multivalent ligand. By contrast, modelling studies have shown that receptor cross-linking by a trivalent ligand may lead to the formation of large receptor superaggregates that may potentially give rise to hyperactive cellular responses. In this work, we have developed a Brownian dynamics-based spatio-temporal model to analyse Fc<i>ɛ</i>RI aggregation by a trivalent antigen. Unlike the existing models, which implemented non-spatial simulation approaches, our model explicitly accounts for the coarse-grained site-specific features of the multivalent species (molecules and complexes). The model incorporates membrane diffusion, steric collisions and sub-nanometre-scale site-specific interaction of the time-evolving species of arbitrary structures. Using the model, we investigated temporal evolution of the species and their diffusivities. Consistent with a recent experimental report, our model predicted sharp decay in species mobility in the plasma membrane in response receptor cross-linking by a multivalent antigen. We show that, due to such decay in the species mobility, post-stimulation receptor aggregation may become self-limiting. Our analysis reveals a potential regulatory mechanism suppressing hyperactivation of immune cells in response to multivalent antigens.
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Date   2018-09-20
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