Many mathematical representations of cellular behavior rely on abstractions that do not account for how macromolecules are organized and move within the crowded cell milieu. For example, linear algebra- and differential equation-based models typically do not represent individual biomolecules or their spatial position and motion. For many questions in biology these simpler models have been sufficient. However, gaps in understanding of many cell functions persist; physics may provide a bridge to close such gaps. I will discuss our progress in developing computational and theoretical tools to model spherically confined colloidal suspensions, as a simple model cell, so that biomolecules and their interactions can be physically represented, individually and explicitly. By developing a more robust and physics-based model for how macromolecules interact within cells we can contribute to a more physically complete representation of living matter. A primary challenge in models of confined colloidal suspensions is the accurate and efficient representation of many-body hydrodynamic interactions, Brownian motion, and the enclosure itself. We have developed a “Cellular Stokesian dynamics” framework that accounts for spherically confined many-body hydrodynamic and lubrication interactions, Brownian motion, and active transport. Utilizing this model, we study diffusion, cooperative motion, and self-organization with confinement and crowding levels representative of a cell interior. I will discuss the qualitative influence of hydrodynamics, confinement and crowding, as well as the consequences of neglecting such influences. Connections to underlying structure are made, and implications for cellular function are discussed.

Modeling the Brownian hydrodynamics of intracellular motion

2019 Spring National Meeting

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