Mesoscale Heterogeneity Shapes Molecular Selectivity and Transport in Biomolecular Condensates
Year: 2026
Type: preprint
Abstract: Growing experimental and computational evidence suggests that many condensates exhibit heterogeneous internal organization at mesoscopic length scales. How such mesoscale organization influences client selectivity and transport, however, remains poorly understood. Here, we use coarse-grained molecular dynamics simulations to compare homogeneous and heterogeneous sticker-spacer condensates with matched scaffold density, sticker fraction, and sticker-sticker interaction strength. We find that the two condensates exhibit markedly different client partitioning profiles and transport dynamics. In the heterogeneous condensate, clients sample distinct local microenvironments in a size-dependent manner, leading to pronounced differences in their transfer free energy compared with the homogeneous condensate. The heterogeneous internal organization also generates local environments with different mobilities and constraints, giving rise to transient subdiffusion and non-Gaussian displacement distributions in client motion. Our results identify mesoscale organization as an important physical factor controlling both molecular selectivity and transport in biomolecular condensates, with implications for the biochemical functions of both natural and engineered systems.
Authors: Vladimir Grigorev, Yaojun Zhang
Institution: Johns Hopkins University
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: Alfred P. Sloan Foundation
Award: G3792763473
OpenAlex ID: W7211934699