Active Transport as a Mechanism of Microphase Selection in Biomolecular Condensates

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.