William Smith

Due to the complexity inherent in biological systems, many particles involved exhibit complicated spatiotemporal dynamics that go beyond the standard models of diffusion of molecules and dynamics of polymers. Here, we investigate two examples of this: the dynamics of intrinsically disordered proteins, and the diffusion of a probe particle in a bacterial cell.

Intrinsically  disordered proteins (IDPs) are a class of proteins that do not possess well-defined three-dimensional  structures in solution under physiological conditions. We have developed all-atom, united-atom, and coarse-grained Langevin dynamics sim- ulations for the IDP α-synuclein that include geometric, attractive hydrophobic, and screened electrostatic interactions and are calibrated to the inter-residue separations measured in recent single-molecule fluorescence energy transfer (smFRET) experiments. We find that α-synuclein is disordered, with conformational statistics that are inter- mediate between random walk and collapsed globule behavior.  We  then show the equivalence of these three models, and apply the coarse-grained model to a set of five IDPs for which smFRET data is available, and identify a strong correlation between the distance to the dividing line between folded proteins and IDPs in the mean charge and hydrophobicity space and the scaling exponent of the radius of gyration with chemical distance along the protein.

Recent  experiments  have also shown that  probe particles in the cytoplasm of E. coli can exhibit sub-diffusive behavior. These cells contain molecules of sizes differing by orders of magnitude, and so we first investigate the effects of this polydispersity on crowding behavior. we show that for bidisperse packings of particle species significantly different in size (diameter ratio r 2: 3), the participation of the smaller species in the packing is dependent on the total volume ratio of the two species, and that the dividing line can be predicted by geometric arguments.  Previous studies have hypothesized that this sub-diffusive behavior could arise from either crowding in the cellular cytoplasm or the metabolic activity  of the living cell. we employ simulations on active matter in solution to demonstrate that while active matter can lead to sub-diffusive behavior, the energy scales required  to do so lead to a significantly raised temperature that would be noticeable in any experimental configuration, and therefore that this is not a significant effect in cells. Similarly, we show that confinement in a colloidal suspension such as the cytoplasm can lead to sub-diffusive and highly non-Gaussian behavior, and lead to a bimodal distribution of step sizes that provide evidence for the cooperative relaxation hypothesis commonly  discussed in the colloidal community.