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

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.