On the importance of the diffusivity gradient term in Brownian dynamics simulations

In a recent study, Garner et al. investigated diffusion in the cytoplasm of fission yeasts, revealing vast heterogeneity in intracellular viscosity. Their conclusion was based on a combination of single-particle-tracking experiments and Brownian dynamics simulations. However, in their simulations, the diffusivity gradient term has been neglected-an assumption common in some biophysical applications but unjustified in this particular case due to spatial variations in diffusivity. Here, we aim to comment on the importance of the diffusivity gradient term and the physical consequences of not including it. We also demonstrate that omitting this term likely leads to overestimating fission yeast intracellular viscosity variance and underestimating its mean. Additionally, we propose modifications to the simulations to incorporate the gradient term.