Mesoscale approaches to modeling eukaryotic cells using MEDYAN

One of the key unsolved challenges at the interface of physical and life sciences is to develop comprehensive computational models of eukaryotic cells grounded in microscopic molecular principles of chemistry and physics. Toward this goal, we developed a reactive mechanochemical force field and software, MEDYAN (Mechanochemical Dynamics of Active Networks: http://medyan.org), which enables simulations of multi-micron cytosolic/cytoskeletal dynamics over ~1000 s timescales. To move beyond mechanics alone toward cell decision-making and toxicity, we are coupling MEDYAN to intracellular signaling kinetics governing proliferation, apoptosis, and differentiation. We are constructing an integrated signaling pathway model with >1000 molecular species to connect molecular-scale reaction networks to emergent cellular phenotypes and toxicity-relevant perturbations. I will outline key challenges in parameterization, validation, and scaling needed for predictive, physics-grounded simulations of eukaryotic cells.