Switching timescale for bistable phase-separation sensing

Determine the timescale and its controlling physical determinants for passive phase-separation dynamics to drive a transition from a state comprising exclusively A-rich droplets to a state dominated by A′-rich droplets in a system of two ternary mixtures (functional components A and A′ and a common scaffold S, with S exchanged between subsystems but no exchange of A or A′). Characterize how this switching timescale relates to finite-time nucleation-and-growth sensing timescales in ternary mixtures and to the timescales of other bistable switching mechanisms (such as genetic toggle switches).

Background

The paper develops a dynamical theory for nucleation-and-growth of droplets in a ternary mixture comprising functional molecules A, scaffold molecules S, and solvent, and analyzes sensing strategies based on phase separation. It shows that coupling two subsystems and exchanging S can enhance sensitivity, and that replenishing A/A′ can yield winner-take-all behavior for robust finite-time decisions.

Building on these results, the authors propose exploring bistable switching behavior analogous to genetic toggle switches, where the system transitions between states dominated by different droplet species. They highlight the need to understand the physical determinants and magnitude of the switching time when conditions change to favor droplets of the other species, and how that timescale compares to the finite-time sensing limits established in their phase-separation framework and to other bistable mechanisms.

References

Physically, what sets the timescale for a system initialised with all $A$-droplets to transition to a state dominated by $A'$-droplets through passive phase separation dynamics? Quantifying how these timescales relate to those of the current work and other bistable mechanisms remains an open problem, but could further establish phase separation as a fast, robust and reliable sensing mechanism.

Optimal sensing through phase separation  (2507.19021 - Alston et al., 25 Jul 2025) in Discussion, final paragraph (referencing Fig. 5c)