Scaffold Affinity Tunes Biomolecular Condensate Function
- 1University of Washington
Abstract
Biomolecular condensates (BMCs) organize cellular biochemistry by concentrating selected molecules into dynamic membrane-free compartments. Yet the molecular parameters that determine not only whether condensates form, but also how they behave and what they do, remain poorly defined. Here we show that scaffold binding affinity (Kd) is a quantitative determinant of condensate phase behavior, internal dynamics and biochemical output. Using a modular SUMO-SIM system in which scaffold valency was held constant while binding affinity was systematically varied, we found that affinity governs the phase boundary, resistance to chemical perturbation, and molecular mobility of condensates in vitro and in human cells. In multicomponent mixtures, the highest-affinity scaffold dominated dense-phase composition and dynamics, revealing a hierarchical rule for condensate organization. Finally, affinity-dependent changes in condensate dynamics translated into tunable enzyme activity, establishing binding energetics as an engineerable parameter for programming condensate biochemistry.
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BibTeX
@misc{reyna2026scaffold,
title = {{Scaffold Affinity Tunes Biomolecular Condensate Function}},
author = {A. Reyna and M. O. Briggs and A. Russell and T. M. Phan and R. J. Wang and R. Allen and T. R. Hinds and N. Zheng and J. Mittal and C. Chatterjee},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.30.748146},
url = {https://www.biorxiv.org/content/10.64898/2026.08.30.748146v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Scaffold Affinity Tunes Biomolecular Condensate Function
AU - A. Reyna
AU - M. O. Briggs
AU - A. Russell
AU - T. M. Phan
AU - R. J. Wang
AU - R. Allen
AU - T. R. Hinds
AU - N. Zheng
AU - J. Mittal
AU - C. Chatterjee
PY - 2026
DA - 2026/08/30
PB - bioRxiv
DO - 10.64898/2026.08.30.748146
UR - https://www.biorxiv.org/content/10.64898/2026.08.30.748146v1
AB - Biomolecular condensates (BMCs) organize cellular biochemistry by concentrating selected molecules into dynamic membrane-free compartments. Yet the molecular parameters that determine not only whether condensates form, but also how they behave and what they do, remain poorly defined. Here we show that scaffold binding affinity (Kd) is a quantitative determinant of condensate phase behavior, internal dynamics and biochemical output. Using a modular SUMO-SIM system in which scaffold valency was held constant while binding affinity was systematically varied, we found that affinity governs the phase boundary, resistance to chemical perturbation, and molecular mobility of condensates in vitro and in human cells. In multicomponent mixtures, the highest-affinity scaffold dominated dense-phase composition and dynamics, revealing a hierarchical rule for condensate organization. Finally, affinity-dependent changes in condensate dynamics translated into tunable enzyme activity, establishing binding energetics as an engineerable parameter for programming condensate biochemistry.
ER -