Colloidal hydrodynamics of the bacterial nucleoid and its impact on diffusion and spatial organization in the cytoplasm*

Computational modeling of the intracellular milieu as a suspension of colloidal macromolecules provides a complementary framework for studying biological cells by providing access to an expanded range of length- and timescales.  Colloidal-scale physics bridge the gap between structural biology, which gives atomistic detail but little time evolution, and systems biology, which models whole-cell time scales but can abstract away spatial effects entirely. Modeling at this colloidal scale led to recent discovery that physical transport regulates some intracellular processes, such as translation elongation in E. Coli. It was recently hypothesized that the nucleoid plays a central role in the organization of macromolecules in the cell, but experimental verification by tracking macromolecular motion is challenging.  In the present work, we study the colloidal hydrodynamics and organization of biomolecules migrating through and surrounding the bacterial nucleoid, with a focus on its structure as a porous medium that acts as a sieve and dynamic regulator by screening migration by size and hindering the diffusion of cellular biomolecules. To do so, we developed a computational model of a simple bacterial cell that explicitly represents the nucleoid, the cell membrane, and macromolecules diffusing inside and outside the nucleoid.  We tracked detailed trajectories, diffusion, and distributions of biomolecules in cytoplasm and how these are affected by macromolecular crowding, size polydispersity, and physical properties of the nucleoid, such as its density, volume, and porosity.  We find spatially heterogeneous organization and particle dynamics that help explain intracellular processes such as protein polarization, translation-elongation, and the diffusion of lipids and RNA into the nucleoid.