Computational Modeling of Protein Dynamics in Eukaryotic Cells

Abstract

Proteins have important functions inside the cell, traveling diffusively or being actively transported to various cellular sites where their activity is needed. Protein motion in the cellular environment is therefore an important topic to understand. However, the cell provides a very complex environment for that motion, which poses problems especially for any modeling effort designed to interpret experimentally observed features. So as to gain a realistic picture of protein dynamics inside the cell, we have recently introduced advanced numerical methods for describing that dynamics [1]. The starting point is an accurate numerical duplicate of the cell determined by LSCM, which can be used as a simulation geometry. Interpreting the internal cellular structures that obstruct the protein motion as the solid component of a porous structure, and treating the motion in the same way as in the case of a porous medium (distinction between effective and apparent diffusion), we can rather accurately take into account the cellular environment in which the motion takes place. The numerical simulations of protein motion in the model cell are based on the lattice-Boltzmann method. Here we use these methods to exactly reproduce photobleaching experiments on the diffusion of Enhanced Yellow Fluorescent Protein (EYFP) in HeLa cells. Comparison of simulated and real experiments can be used to characterize protein motion and the related diffusion coefficients. We pay particular attention to the nuclear translocation of EYFP in these cells.[1] Kuhn T., Ihalainen T. O., Hyvaluoma J., Dross N., Willman S. F., Langovski J., Vihinen-Ranta M. and Timonen J. 2011 Protein Diffusion in Mammalian Cell Cytoplasm. PLoS ONE 6(8): e22962.