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Active transport as a mechanism of microphase selection in biomolecular condensates

Le Qiao1,*, Peter Gispert1, Lukas S. Stelzl2,3, and Friederike Schmid1,†

  • *Contact author: le.qiao@uni-mainz.de
  • †Contact author: friederike.schmid@uni-mainz.de

Phys. Rev. Research 8, 033345 – Published 21 September, 2026

DOI: https://doi.org/10.1103/wk2j-3bz9

Abstract

The size and organization of biomolecular condensates formed by liquid-liquid phase separation are set by multiple cellular mechanisms that are not yet fully understood. Here, we identify a transport-driven mechanism: 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∼b−1/4) from a few hundred nanometers up to the micron scale. The selected length scale is robust to the intrinsic shot noise of the binding-release reactions. In anisotropic cytoskeletal environments, transport asymmetry drives morphological transitions from spherical to cylindrical condensates, independently of the thermodynamic parameters. This mechanism provides a versatile, spatiotemporally programmable route to condensate organization and informs the design of synthetic active emulsions with tunable architectures.

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