Towards cell scale agent-based models for membrane cytoskeleton interactions

The cytoskeleton is a dynamic far-from-equilibrium polymer network. It consumes energy to do mechanical work, and it interacts with complex chemical reaction networks in the cytoplasm and cell membrane to organize into various structures. We will discuss how the MEDYAN (medyan.org) model and software can simulate the chemical and mechanical interactions of actin filaments, crosslinks, myosin motor proteins, and membranes at the micrometer length scale and minute time scale. The next generation of MEDYAN is written in the Julia programming language (MEDYAN.jl). It has significant performance improvements including a 10x faster cylinder volume exclusion algorithm and a 10x faster Gillespie implementation for scheduling chemical reaction events. In addition, it includes an HDF5-based snapshot format that stores the full state of the simulation and enables restarts, and detailed linker and filament aging reactions that have reaction rates that adjust to changes to local monomer states, linker states, and linker mechanics. More complex reactions and reaction rates can be added using user-defined reaction callbacks. It also includes a deformable mesh-based membrane model. MEDYAN.jl is being used to study the role of ARP2/3 in the actin structure in the core of an axon growth cone. MEDYAN.jl is also being used to prototype models of membrane cytoskeleton chemical and mechanical interactions, including activation of ARP2/3.