InterCells: A Generic Monte-Carlo Simulation of Intercellular Interfaces Captures Nanoscale Patterning at the Immune...

Area of Science:

• Computational Biology and Biophysics
• Immunology and Cell Biology

Background:

• Cellular interfaces, such as immune synapses (ISs), are crucial for intercellular communication, regulating functions like development and immune responses.
• Understanding molecular organization and dynamics at these interfaces is key to deciphering cellular signaling.

Purpose of the Study:

• To introduce a versatile agent-based Monte Carlo simulation for modeling user-defined cellular interfaces.
• To investigate molecular patterning and dynamics within early T cell immune synapses (ISs).

Main Methods:

• Development of an agent-based Monte Carlo simulation incorporating membrane molecule diffusion, interaction, and plasma membrane biophysics.
• Validation using three-color single molecule localization microscopy (SMLM) to observe molecular patterns in T cell contacts.
• Application of the simulation to study patterning dynamics under experimental conditions and with antigen-presenting cells (APCs).

Main Results:

• The simulation accurately captures the topography and energetics of plasma membranes at intercellular contacts.
• Experimental data revealed intricate mutual patterning of T cell antigen receptors (TCRs), integrins, and glycoproteins in early T cell contacts.
• Simulation predictions successfully reproduced the observed molecular patterning dynamics in T cell-APC interactions.

Conclusions:

• The developed simulation provides a generic and powerful tool for studying realistic cell-cell interfaces.
• This computational approach facilitates hypothesis testing and iterative experimental design for cell-cell interaction studies.
• The findings highlight the complex molecular organization within early immune synapses.