Sticky interactions govern sequence-dependent dynamics in biomolecular condensates

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Authors: Keerthivasan Muthukumar, Dinesh Sundaravadivelu Devarajan, Young Ho Kim, Jeetain Mittal
Cited by: 4
References: 90

Abstract

Intrinsically disordered proteins (IDPs) play a central role in shaping the dynamics and material properties of biomolecular condensates. Understanding how sequence features determine these properties is critical for elucidating physiological function and guiding the rational design of synthetic condensates. Here, we use molecular dynamics simulations to investigate condensates formed by model IDPs with systematically varied chain length and charge patterning, two features characteristic of natural IDPs. Our results show that chain relaxation times, governed by sequence-dependent electrostatic interactions, quantitatively predict condensate viscosity and diffusivity. These condensates exhibit dynamics consistent with a crossover regime between Rouse and reptation behavior. While the Rouse model with idealized friction fails to capture sequence effects, a sticky Rouse-like framework, which incorporates transient interchain contact lifetimes, accurately predicts chain reconfiguration times and, consequently, macroscopic material properties. This work establishes a predictive, sequence-resolved framework that links molecular interactions to condensate dynamics across length and time scales.

Fields of Study & Subjects

Protein Structure and Dynamics Force Microscopy Techniques and Applications Bacteriophages and microbial interactions

Publication details

Journal / source
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Volume
123
Issue
1
Pages
e2518384122–e2518384122
Publication date
2 January 2026
Language
EN