Coupling Molecular and Cellular Dynamics in a Large-Scale Monte Carlo Simulation

TL;DR

This paper introduces a new simulation method that links molecular interactions with cell shape changes, enabling more realistic modeling of cellular processes.

Contribution

The novel extension of MCell4 allows bidirectional feedback between molecular dynamics and cell morphology.

Findings

The simulation platform now supports dynamic coupling of molecular interactions and membrane changes.

The model successfully simulates T cell spreading on antigen-presenting surfaces.

The approach captures correlations between molecular interactions and cell surface dynamics.

Abstract

Cells change their shape to survive, proliferate, and function. Such changes are both driven by stochastic molecular interactions and affect them in return. Recent Monte-Carlo simulations, such as MCell4, can explicitly capture the interactions of millions of molecules, yet cannot dynamically couple these interactions with changes in morphology. Here, we extend the MCell4 simulation platform by incorporating physical forces that allow bidirectional feedback between dynamic molecular interactions and outer or intracellular membranes. We start with some simple examples such as a moving piston and a fluctuating membrane. We then simulate the spreading of T cells on antigen-presenting cells or an activating surface due to cognate interactions of surface molecules, such as receptors and their ligands or integrins. The coupled simulation quantitatively accounts for the expected correlation of molecular interactions and the spreading dynamics of the cell surface. Thus, our approach provides a versatile foundation for simulating a variety of dynamic cell systems and processes.

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