Dissertation Defense: Wendell Smith, Yale University, “Modeling Diffusion and Motion in Cells at the Molecular Level”

Event time: 
Friday, March 4, 2016 - 1:00pm to 2:00pm
Mason Laboratory (ML), 104 See map
9 Hillhouse Ave.
New Haven, CT 06511
(Location is wheelchair accessible)
Event description: 

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 simula- tions for IDPs that are calibrated to quantitative experiments. We show the equivalence of these three models, and apply the coarse-grained model to a set of five IDPs, 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 expo- nent 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. We investigate three possible explanations for this behavior: the high polydispersity involved in a cell, activity due to metabolism, and the effects of crowding on dynamics. From this research, we find that in a bidisperse system with particles of significantly different sizes (diameter ratio r 2: 3), the behavior of the two species in the packing is separable and somewhat independent of the other species. We then employ simulations on active matter in solution to demonstrate that while active matter can lead to sub-diffusive behavior, the energy required to do so is not physiologically feasible. Similarly, we show that confinement in a colloidal suspension such as the cytoplasm can lead to sub-diffusive and highly non-Gaussian behavior.