Integrating spatial biophysical simulations across scales and methods.

Abstract

The Allen Institute for Cell Science aims to understand the principles by which human induced pluripotent stem cells (hiPSCs) establish and maintain robust dynamic localization of cellular structures, and how they transition between states during differentiation and disease. The Simularium project aims to involve the wider biology community, especially wet lab biologists, in building and analyzing spatial mechanistic simulations at different levels of scale, and connecting them in the context of whole cells. We have composed multiple types of models that simulate objects in 3D space at multiple time and length scales and with different representations, in order to compare their behavior and outputs. To connect these models we have built interfaces using the Vivarium simulation framework, which allows for the flexible composition of many different models, and we are aiming to build multiscale models with adaptive resolution and calculation methods. To demonstrate this approach for actin dynamics, we have built interfaces between the community software engines ReaDDy, Cytosim, and MEDYAN, so that the composed model can be configured to simulate actin fibers either with coarse-grained monomers or filament lines. We have defined simple models that can translate between each of these simulation engines as unit tests for physical properties that are required for more complex models of endocytosis and leading edge dynamics of crawling cells. These test models explore how actin properties like bend and twist coupling, persistence length, and force generation differ when simulated with different methods and in different parameter regimes. We visualize the outputs interactively in 3D using the web-based Simularium viewer to explore differences between models and the implications for reproducible modeling of actin filaments across scales and methods.