Theoretical limits for sensing through phase separation

• 成果类型: Article
• 署名作者: Alston, Henry; Rouches, Mason; Murugan, Arvind; Walczak, Aleksandra M.; Mora, Thierry
• 署名单位: Sorbonne Universite; Universite PSL; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Ecole Normale Superieure (ENS); Universite Paris Cite; University of Chicago
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2520040123
• 发表日期: 2026-02-10
• 页码: 2520040123
• 关键词: liquid-liquid phase transition; cellular decision-making; droplet; biological concentration sensing; covalent modification; ULTRASENSITIVITY; nucleation; droplets; MODEL

摘要

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 cyclic GMP-AMP synthase 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.