Liquid-like condensates that bind actin promote assembly and bundling of actin filaments

Caleb Walker¹, Aravind Chandrasekaran², Daniel Mansour², Kristin Graham³, Andrea Torres¹, Liping Wang⁴, Eileen M Lafer⁴, Padmini Rangamani⁵, Jeanne C Stachowiak⁶

Affiliations

¹ Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
² Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA, USA.
³ Cell and Molecular Biology, The University of Texas at Austin, Austin, TX, USA.
⁴ Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
⁵ Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA, USA; Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA. Electronic address: prangamani@ucsd.edu.
⁶ Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA; Chemical Engineering, The University of Texas at Austin, Austin, TX, USA. Electronic address: jcstach@austin.utexas.edu.

PMID: 39914390
PMCID: PMC12151779 (available on 2026-06-09)
DOI: 10.1016/j.devcel.2025.01.012

Liquid-like condensates that bind actin promote assembly and bundling of actin filaments

Caleb Walker et al. Dev Cell. 2025.

. 2025 Jun 9;60(11):1550-1567.e4.

doi: 10.1016/j.devcel.2025.01.012. Epub 2025 Feb 5.

Authors

Caleb Walker¹, Aravind Chandrasekaran², Daniel Mansour², Kristin Graham³, Andrea Torres¹, Liping Wang⁴, Eileen M Lafer⁴, Padmini Rangamani⁵, Jeanne C Stachowiak⁶

Affiliations

¹ Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
² Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA, USA.
³ Cell and Molecular Biology, The University of Texas at Austin, Austin, TX, USA.
⁴ Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
⁵ Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA, USA; Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA, USA. Electronic address: prangamani@ucsd.edu.
⁶ Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA; Chemical Engineering, The University of Texas at Austin, Austin, TX, USA. Electronic address: jcstach@austin.utexas.edu.

PMID: 39914390
PMCID: PMC12151779 (available on 2026-06-09)
DOI: 10.1016/j.devcel.2025.01.012

Abstract

Biomolecular condensates perform diverse physiological functions. Previous work showed that VASP, a processive actin polymerase, forms condensates that assemble and bundle actin. Here, we show that this behavior does not require proteins with specific polymerase activity. Specifically, condensates composed of Lamellipodin, a protein that binds actin but is not an actin polymerase, were also capable of assembling actin filaments. To probe the minimum requirements for condensate-mediated actin bundling, we developed an agent-based computational model. Guided by its predictions, we hypothesized that any condensate-forming protein that binds filamentous actin could bundle filaments through multivalent crosslinking. To test this, we added a filamentous-actin-binding motif to Eps15, a condensate-forming protein that does not normally bind actin. The resulting chimera formed condensates that facilitated efficient assembly and bundling of actin filaments. Collectively, these findings broaden the family of proteins that could organize cytoskeletal filaments to include any filamentous-actin-binding protein that participates in protein condensation.

Keywords: Lamellipodin; VASP; actin cytoskeleton; agent-based modeling; biomolecular condensates; multivalent interactions; protein phase separation.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Update of

Liquid-like condensates that bind actin drive filament polymerization and bundling.
Walker C, Chandrasekaran A, Mansour D, Graham K, Torres A, Wang L, Lafer EM, Rangamani P, Stachowiak JC. Walker C, et al. bioRxiv [Preprint]. 2024 May 22:2024.05.04.592527. doi: 10.1101/2024.05.04.592527. bioRxiv. 2024. Update in: Dev Cell. 2025 Jun 9;60(11):1550-1567.e4. doi: 10.1016/j.devcel.2025.01.012. PMID: 38826190 Free PMC article. Updated. Preprint.

References

1. Fletcher DA, and Mullins RD (2010). Cell mechanics and the cytoskeleton. Nature 463, 485–492. 10.1038/nature08908. - DOI - PMC - PubMed
1. Hinze C, and Boucrot E (2018). Local actin polymerization during endocytic carrier formation. Biochem. Soc. Trans. 46, 565–576. 10.1042/BST20170355. - DOI - PubMed
1. Pollard TD, and Cooper JA (2009). Actin, a Central Player in Cell Shape and Movement. Science 326, 1208–1212. 10.1126/science.1175862. - DOI - PMC - PubMed
1. Vasioukhin V, Bauer C, Yin M, and Fuchs E (2000). Directed Actin Polymerization Is the Driving Force for Epithelial Cell–Cell Adhesion. Cell 100, 209–219. 10.1016/S0092-8674(00)81559-7. - DOI - PubMed
1. Campellone KG, and Welch MD (2010). A nucleator arms race: cellular control of actin assembly. Nat. Rev. Mol. Cell Biol. 11, 237–251. 10.1038/nrm2867. - DOI - PMC - PubMed

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Liquid-like condensates that bind actin promote assembly and bundling of actin filaments

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Liquid-like condensates that bind actin promote assembly and bundling of actin filaments

Authors

Affiliations

Abstract

Conflict of interest statement

Update of

References

MeSH terms

Substances

Grants and funding

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Full Text Sources

Miscellaneous