Intrinsically disordered proteins (IDPs) can undergo liquid–liquid phase separation and coacervation, producing biomolecular condensates with diverse structural and rheological properties. The interplay between sequence-dependent electrostatic interactions and conformational heterogeneity gives rise to complex behavior spanning molecular to macroscopic scales. In this talk, I will present recent advances from my group that integrate physics-based simulations with experimental measurements to reveal how molecular driving forces shape condensate structure, dynamics, and material response. Our recent study demonstrated that dilute-phase conformations are predictive of condensate mechanics, providing a framework for connecting single-chain behavior to bulk properties1. Building on this, our latest work extends to understanding internal condensate dynamics across length and time scales, revealing how local motions and interactions contribute to emergent macroscopic behavior2. Together, these results offer a multiscale picture linking microscopic organization and interactions to macroscopic flow and relaxation, with implications for both natural biological assemblies and engineered soft materials.
References
[1] Sundaravadivelu Devarajan, D., Wang, J., Szała-Mendyk, B., Rekhi, S., Nikoubashman, A., Kim, Y. C., & Mittal, J. (2024). Sequence-dependent material properties of biomolecular condensates and their relation to dilute phase conformations. Nature Communications, 15(1), 1912.
[2] Muthukumar, K., Devarajan, D. S., Kim, Y. C., & Mittal, J. (2025). Sticky Interactions Govern Sequence-Dependent Dynamics in Biomolecular Condensates. bioRxiv, 2025-07.