Mesoscale Heterogeneity Shapes Molecular Selectivity and Transport in Biomolecular Condensates
- 1Johns Hopkins University
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.
Related
- Molecular determinants of arginine versus lysine cation–π interactions in biomolecular condensates
- Long-range transport of biomolecular condensates by Marangoni effect
- Disulfide Crosslink Density is a Key Determinant in the Formation, Dynamics, and Maturation of Cysteine-rich Designer Biomolecular Condensates.
- e^-2 Threshold for Bistability in Non-equilibrium Sorting of Biomolecular Condensates
- Biomolecular condensates can function as inherent catalysts
BibTeX
@misc{grigorev2026mesoscale,
title = {{Mesoscale Heterogeneity Shapes Molecular Selectivity and Transport in Biomolecular Condensates}},
author = {V. Grigorev and Y. Zhang},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.05.749622},
url = {https://www.biorxiv.org/content/10.64898/2026.09.05.749622v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Mesoscale Heterogeneity Shapes Molecular Selectivity and Transport in Biomolecular Condensates
AU - V. Grigorev
AU - Y. Zhang
PY - 2026
DA - 2026/09/05
PB - bioRxiv
DO - 10.64898/2026.09.05.749622
UR - https://www.biorxiv.org/content/10.64898/2026.09.05.749622v1
AB - 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.
ER -