Collaborative Research: Mesoscopic properties of multi-phase biomolecular liquids

NON TECHNICAL ABSTRACT: Living cells organize their chemistry using tiny liquid droplets made from biological molecules. These droplets gather certain molecules, help reactions occur, and modify their shape as conditions change. Cells can contain multiple types of liquid droplets, and those different types can be arranged in complex structures. We do not know how these structures form or how many different liquids can exist together. This project will study the physical rules that control how such liquid compartments form and organize. The work will use a programmable system built from DNA to create and study these droplets. The research will show how molecular design choices set the number of liquids and how they interact. It will also explain how complex droplet structures emerge from these interactions. The project will combine laboratory experiments with computer models to guide material design. The results will advance basic knowledge in biology and materials science. The results will also support the development of future biotechnologies, such as those that use liquid droplets to carry out chemical reactions. The project will also train graduate and undergraduate students in cross-disciplinary research skills needed for the future workforce. TECHNICAL ABSTRACT: This project will conduct a combined experimental and theoretical investigation of the physics of multiphase biomolecular liquids and the complex mesoscale droplet morphologies they form. Motivated by multiphase condensates observed in living cells, the research will address three central questions: how many distinct biomolecular liquid phases can coexist simultaneously, how microscopic molecular properties determine phase and interfacial behavior, and how equilibrium and kinetic processes govern droplet morphology. Experiments will use programmable DNA nanostar particles that assemble into liquid droplets through sequence-specific interactions. By exploiting DNA sequence orthogonality and tunable particle design parameters, the project will construct libraries of mutually immiscible liquid phases and quantify their phase behavior and interfacial properties. Advanced fluorescence microscopy will be used to characterize droplet composition, surface tensions, and assembly dynamics. In parallel, coarse-grained molecular dynamics simulations and mesoscale thermodynamic models will be developed to link particle-level parameters—such as valence, flexibility, electrostatics, and binding specificity—to macroscopic phase behavior and interfacial tensions. These models will be validated against experimental measurements and extended to predict and design complex droplet morphologies, including Janus and droplet-in-droplet structures. The project will also explore kinetic pathways and sequence-dependent assembly protocols that enable controlled access to otherwise inaccessible structures. The expected intellectual contribution is a predictive, experimentally validated framework for understanding and designing multiphase biomolecular liquids, with broad relevance to soft matter physics, biomolecular condensates, and programmable materials. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2414345 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Omar Saleh | Institution: University of California-Santa Barbara, SANTA BARBARA, CA | Award Amount: $514,198 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2414345 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2414345.html