Theoretical limits for sensing through phase separation

TL;DR

This paper models how phase separation in cells enables rapid, sensitive detection of small environmental changes, providing a theoretical framework for understanding biomolecular condensate-based sensing.

Contribution

It introduces a dynamical model of droplet nucleation and growth to explain how phase separation enhances cellular sensing capabilities.

Findings

Cells can detect 1% concentration differences within minutes.

Optimal sensing protocols leverage the sharp phase separation transition.

Phase separation offers a rapid alternative to classical biochemical sensing.

Abstract

Biomolecular condensates form on timescales of seconds in cells upon environmental or compositional changes. Condensate formation is thus argued to act as a mechanism for sensing such changes and quickly initiating downstream processes, such as forming stress granules in response to heat stress and amplifying cGAS enzymatic activity upon detection of cytosolic DNA. Here, we study a dynamical model of droplet nucleation and growth to demonstrate how phase separation allows cells to discriminate small concentration differences on finite, biologically relevant timescales. We propose optimal sensing protocols, which use the sharp onset of phase separation. We show how, given experimentally measured rates, cells can achieve rapid and robust sensing of concentration differences of 1% on a timescale of minutes, offering an alternative to classical biochemical mechanisms.