Controlled and orthogonal partitioning of large particles into biomolecular condensates

Fleurie M. Kelley, Anas Ani, Emily G. Pinlac, Bridget Linders, Bruna Favetta, Mayur Barai, Yuchen Ma, Arjun Singh, Gregory L. Dignon (), Yuwei Gu () and Benjamin S. Schuster ()
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Fleurie M. Kelley: Rutgers, The State University of New Jersey
Anas Ani: Rutgers, The State University of New Jersey
Emily G. Pinlac: Rutgers, The State University of New Jersey
Bridget Linders: Rutgers, The State University of New Jersey
Bruna Favetta: Rutgers, The State University of New Jersey
Mayur Barai: Rutgers, The State University of New Jersey
Yuchen Ma: Rutgers, The State University of New Jersey
Arjun Singh: Rutgers, The State University of New Jersey
Gregory L. Dignon: Rutgers, The State University of New Jersey
Yuwei Gu: Rutgers, The State University of New Jersey
Benjamin S. Schuster: Rutgers, The State University of New Jersey

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Partitioning of client molecules into biomolecular condensates is critical for regulating the composition and function of condensates. Previous studies suggest that client size limits partitioning. Here, we ask whether large clients, such as macromolecular complexes and nanoparticles, can partition into condensates based on particle-condensate interactions. We seek to discover the fundamental biophysical principles that govern particle inclusion in or exclusion from condensates, using polymer nanoparticles surface-functionalized with biotin or oligonucleotides. Based on our experiments, coarse-grained molecular dynamics simulations, and theory, we conclude that arbitrarily large particles can controllably partition into condensates given sufficiently strong condensate-particle interactions. Remarkably, we also observe that beads with distinct surface chemistries partition orthogonally into immiscible condensates. These findings may provide insights into how various cellular processes are achieved based on partitioning of large clients into biomolecular condensates, and they offer design principles for drug delivery systems that selectively target disease-related condensates.

Date: 2025
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DOI: 10.1038/s41467-025-58900-5

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