Chemical Reactions regulated by Phase-Separated Condensates

TL;DR

This paper develops a theoretical framework to understand how phase-separated condensates influence chemical reactions, revealing control parameters and optimal conditions for reaction enhancement in biological systems.

Contribution

The authors introduce a decoupled theoretical model that isolates phase separation effects from reaction kinetics, enabling detailed analysis of condensate influence on chemical processes.

Findings

Condensates can optimize reaction yields and rates.

There exists an optimal condensate volume for maximal reaction effects.

The framework aids in quantifying condensate impact on cellular biochemistry.

Abstract

Phase-separated liquid condensates can spatially organize and thereby regulate chemical processes. However, the physicochemical mechanisms underlying such regulation remain elusive as the intramolecular interactions responsible for phase separation give rise to a coupling between diffusion and chemical reactions at non-dilute conditions. Here, we derive a theoretical framework that decouples the phase separation of scaffold molecules from the reaction kinetics of diluted clients. As a result, phase volume and client partitioning coefficients become control parameters, which enables us to dissect the impact of phase-separated condensates on chemical reactions. We apply this framework to two chemical processes and show how condensates affect the yield of reversible chemical reactions and the initial rate of a simple assembly process. In both cases, we find an optimal condensate volume at which the respective chemical reaction property is maximal. Our work can be applied to experimentally quantify how condensed phases alter chemical processes in systems biology and unravel the mechanisms of how biomolecular condensates regulate biochemistry in living cells.