AUTHOR=Neve-Oz Yair , Sajman Julia , Razvag Yair , Sherman Eilon TITLE=InterCells: A Generic Monte-Carlo Simulation of Intercellular Interfaces Captures Nanoscale Patterning at the Immune Synapse JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02051 DOI=10.3389/fimmu.2018.02051 ISSN=1664-3224 ABSTRACT=

Molecular interactions across intercellular interfaces serve to convey information between cells and to trigger appropriate cell functions. Examples include cell development and growth in tissues, neuronal and immune synapses (ISs). Here, we introduce an agent-based Monte-Carlo simulation of user-defined cellular interfaces. The simulation allows for membrane molecules, embedded at intercellular contacts, to diffuse and interact, while capturing the topography and energetics of the plasma membranes of the interface. We provide a detailed example related to pattern formation in the early IS. Using simulation predictions and three-color single molecule localization microscopy (SMLM), we detected the intricate mutual patterning of T cell antigen receptors (TCRs), integrins and glycoproteins in early T cell contacts with stimulating coverslips. The simulation further captures the dynamics of the patterning under the experimental conditions and at the IS with antigen presenting cells (APCs). Thus, we provide a generic tool for simulating realistic cell-cell interfaces, which can be used for critical hypothesis testing and experimental design in an iterative manner.