Wetting-mediated extracellular phase separation drives long-range cell adhesion

Authors

Wang, A., Yang, D., Zhang, H., Paunov, V., Tian, S., Dong, L., Tanaka, H., Yuan, J., Wang, C.

Abstract

Cells must efficiently locate and engage for tissue formation and immune coordination, yet classical receptor-ligand binding is limited to nanometre distances and is inherently slow. Here, we uncover a previously unrecognised physical principle, liquid-like adhesion by phase separation (LAPS). This process creates dynamic wetting layers on cell surfaces, functioning as 'liquid bridges' that enable robust, long-range cell capture across tens of micrometres. Remarkably, this wetting- mediated attraction remains effective at nanomolar concentrations-conditions where bulk phase separation would not be expected-and facilitates high-fidelity cell sorting through competitive wetting. By integrating aqueous two-phase systems, endogenous proteins (Galectin-3, CCL5), and fluid-particle-dynamics simulations, we demonstrate that extracellular liquid-liquid phase separation not only mediates long-range cell capture but also acts as a physical catalyst for contact-dependent signaling. These findings establish extracellular phase separation as a key physical principle complementing molecular recognition in multicellular systems, offering new opportunities for understanding immune response, tissue morphogenesis, and therapeutic strategies targeting the extracellular environment.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 27 Jan 2026.

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