Intracellular facilitated diffusion: searchers, crowders and blockers

TL;DR

This paper uses large-scale Brownian dynamics simulations to study how crowding proteins influence the facilitated diffusion process of bacterial regulatory proteins searching for DNA targets, revealing complex effects on search mechanisms.

Contribution

It provides new insights into how different types of crowding proteins uniquely impact the facilitated diffusion search process in bacteria.

Findings

Crowding proteins can act as roadblocks or freely diffusing entities.

Macromolecular crowding significantly alters the balance between 3D and 1D diffusion.

Total search time remains surprisingly robust despite crowding effects.

Abstract

In bacteria, regulatory proteins search for a specific DNA binding target via "facilitated diffusion": a series of rounds of 3D diffusion in the cytoplasm, and 1D linear diffusion along the DNA contour. Using large scale Brownian dynamics simulations we find that each of these steps is affected differently by crowding proteins, which can either be bound to the DNA acting as a road block to the 1D diffusion, or freely diffusing in the cytoplasm. Macromolecular crowding can strongly affect mechanistic features such as the balance between 3D and 1D diffusion, but leads to surprising robustness of the total search time.