Kinetics of polymer looping with macromolecular crowding: effects of volume fraction and crowder size

TL;DR

This study explores how macromolecular crowding influences polymer looping dynamics, revealing that crowder size and volume fraction can either hinder or promote looping, with implications for biological processes like DNA and RNA folding.

Contribution

It provides a detailed analysis of how crowder size and concentration affect polymer looping kinetics, highlighting non-trivial effects and underlying mechanisms.

Findings

Small crowders slow down looping due to increased viscosity.

Large crowders facilitate looping through confinement effects.

Crowding volume fraction and chain length significantly influence kinetics.

Abstract

The looping of polymers such as DNA is a fundamental process in the molecular biology of living cells, whose interior is characterised by a high degree of molecular crowding. We here investigate in detail the looping dynamics of flexible polymer chains in the presence of different degrees of crowding. From the analysis of the looping-unlooping rates and the looping probabilities of the chain ends we show that the presence of small crowders typically slow down the chain dynamics but larger crowders may in fact facilitate the looping. We rationalise these non-trivial and often counterintuitive effects of the crowder size onto the looping kinetics in terms of an effective solution viscosity and standard excluded volume effects. Thus for small crowders the effect of an increased viscosity dominates, while for big crowders we argue that confinement effects (caging) prevail. The tradeoff between both trends can thus result in the impediment or facilitation of polymer looping, depending on the crowder size. We also examine how the crowding volume fraction, chain length, and the attraction strength of the contact groups of the polymer chain affect the looping kinetics and hairpin formation dynamics. Our results are relevant for DNA looping in the absence and presence of protein mediation, DNA hairpin formation, RNA folding, and the folding of polypeptide chains under biologically relevant high-crowding conditions.