Reconstituted nascent adhesion condensates drive actin polymerization on supported lipid bilayers

  • Sci Adv. 2026 May 8;12(19):eaeb6691. doi: 10.1126/sciadv.aeb6691.
Arsenii Hordeichyk  1  2 ,  Kristian A T Pajanonot  1  2 ,  Chiao-Peng Hsu  1 ,  Timon Nast-Kolb  1 ,  Lukas J Neumann  1 ,  Reinhard Fässler  1  3 ,  Andreas R Bausch  1  2
Affiliations
  • 1. Heinz Nixdorf Chair in Biophysical Engineering of Living Matter, Center for Functional Protein Assemblies, Center for Organoid Systems, Department of Bioscience, Technical University of Munich, Technical University of Munich School of Natural Sciences, Garching 85748, Germany.
  • 2. Max Planck School Matter to Life, Heidelberg 69120, Germany.
  • 3. Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
PMID: 42102206 DOI: 10.1126/sciadv.aeb6691
Abstract

Nascent adhesions are early integrin-based assemblies that couple the extracellular matrix to the actin Cytoskeleton and mature into focal adhesions. Many nascent-adhesion proteins interact through weak, multivalent contacts, suggesting that liquid-like organization may contribute to adhesion assembly. However, how phase separation shapes Actin polymerization and organization remains unclear. Here, we compare two vasodilator-stimulated phosphoprotein (VASP)-recruiting adaptor proteins, zyxin and vinculin, to determine how adaptor identity tunes condensate properties and Actin coupling. Both zyxin-VASP and vinculin-VASP assemblies drive Integrin clustering and support Actin filament growth. Notably, zyxin-VASP condensates remain fluid and redistribute along newly formed Actin bundles, whereas vinculin-VASP condensates are more rigid and fail to spread along Actin despite sustaining polymerization. These results suggest that differential VASP recruitment can modulate condensate properties and Actin architecture, providing a potential mechanism for the maturation of nascent adhesions into focal adhesions.

Products