Geometry controls diffusive target encounters and escape in tubular structures

Abstract

The endoplasmic reticulum (ER) is a network of sheet-like and tubular structures that spans much of a cell and contains molecules undergoing diffusive searches for targets, such as unfolded proteins searching for chaperones and recently-folded proteins searching for export sites. By applying a Brownian dynamics algorithm to simulate molecule diffusion, we describe how ER tube geometry influences whether a searcher will encounter a nearby target or instead diffuse away to a region near to a distinct target, as well as the timescale of successful searches. We find that targets are more likely to be found for longer and narrower tubes, and larger targets, and that search in the tube volume is more sensitive to the search geometry compared to search on the tube surface. Our results suggest ER proteins searching for low-density targets in the membrane and the lumen are very likely to encounter the nearest target before diffusing to the vicinity of another target. Our results have implications for the design of target search simulations and calculations and interpretation of molecular trajectories on the ER network, as well as other organelles with tubular geometry.