Dynamic principles of concentration buffering through liquid-liquid phase separation

TL;DR

This study investigates how liquid-liquid phase separation (LLPS) biomolecular condensates dynamically buffer concentration fluctuations, revealing their frequency-dependent filtering properties and establishing principles for their regulation and design.

Contribution

It provides the first systematic frequency-domain analysis of LLPS concentration buffering, linking condensate parameters to their dynamic regulation capabilities.

Findings

Condensates act as frequency-selective filters.

Dense phase attenuates both low- and high-frequency perturbations.

Buffering effectiveness depends on interaction strength, droplet size, and diffusivity.

Abstract

Living systems must maintain robust biochemical function despite fluctuations that span a wide range of timescales. Biomolecular condensates formed by liquid-liquid phase separation (LLPS) have been shown to buffer concentration fluctuations, but the principles governing their dynamic regulation remain unclear. We address this by probing the response of LLPS to oscillatory perturbations that mimic fluctuations across different timescales, establishing the first systematic frequency-domain analysis of concentration buffering by condensates. We find that condensates act as frequency-selective filters: the perturbed dilute phase behaves as a high-pass filter, while the dense phase attenuates both low- and high-frequency perturbations. We establish quantitative links between LLPS parameters including interaction strength, droplet size, and molecular diffusivity, and the timescale range over which condensates effectively buffer concentration fluctuations. These findings establish the fundamental dynamical limits of concentration buffering by LLPS, with implications for how cells may use LLPS to adapt to fluctuating environments and for the design of synthetic condensates with programmable control properties.