Controlled and orthogonal partitioning of large particles into biomolecular condensates.

Biomolecular condensates are subcellular compartments that selectively recruit or exclude client molecules, even though condensates lack an enclosing membrane. Many biochemical reconstitution experiments have investigated mechanisms by which membraneless organelles control partitioning, modeling how cells spatiotemporally recruit components into condensates to regulate cellular functions. One outstanding question is whether partitioning is strictly limited by client size. In this work, we engineered nanoparticles with various sizes and surface functionalities and measured how these variables determine partitioning. We observed controlled and orthogonal partitioning of large particles into several condensate types, driven by strong particle-condensate interactions. Molecular simulations recapitulated key results. Our work advances understanding of how condensate composition is regulated, and our nanoparticle toolbox may also inspire a platform for drug delivery.