Active Transport as a Mechanism of Microphase Selection in Biomolecular Condensates

TL;DR

This paper proposes a transport-driven mechanism involving active redistribution of proteins along cytoskeletal filaments to control the size and shape of biomolecular condensates, independent of thermodynamic factors.

Contribution

It introduces a minimal model showing how active transport can induce microphase separation and shape transitions in condensates, offering a new perspective on cellular organization.

Findings

Transport asymmetry causes shape transitions from spherical to cylindrical condensates.

Controlling motor binding rates or velocities tunes condensate sizes from nanometers to micrometers.

Active transport can arrest coarsening and select finite condensate sizes at low binding fractions.

Abstract

Cells control the size and organization of biomolecular condensates formed by liquid-liquid phase separation (LLPS), but multiple mechanisms likely contribute to this control and remain to be fully elucidated. Here we propose a transport-driven mechanism in which stochastic binding of phase-separating proteins to cytoskeletal motor proteins, followed by active redistribution along filament networks, generates an effective long-range repulsion that arrests coarsening and selects a finite condensate size. A minimal diffusion-transport model, analyzed by linear stability theory and three-dimensional simulations, reveals a transition from macroscopic to microphase separation at remarkably low binding/release fractions, corresponding to minute motor-bound populations. Tuning motor binding rates $b$ or transport velocities enables sublinear control of condensate sizes ($L \sim b^{-1/4}$) from nanometers to micrometers. In anisotropic cytoskeletal environments, transport asymmetry drives morphological transitions from spherical to cylindrical condensates. Operating independently of thermodynamic parameters, this mechanism provides a versatile, spatiotemporally programmable route to condensate organization and informs the design of synthetic active emulsions with tunable architectures.