Sequence-dependent biomolecular phase separation driven by short-range interaction: From material properties to...

Liquid-liquid phase separation (LLPS) of biomacromolecules drives the formation of biomolecular condensates, which possess material properties crucial for various biological functions. While recent studies have primarily focused on LLPS driven by long-range, nonspecific interactions, the role of short-range, one-to-one specific interactions in sequence-dependent behavior still remains elusive. In this study, we combined theoretical analysis and coarse-grained molecular dynamics simulations to systematically investigate the sequence-dependent material properties of biomolecular condensates. By introducing the sequence descriptor ϕ^{*}, we identified strong correlations between ϕ^{*} and key material or structural properties, such as the single-chain radius of gyration, critical temperature, density, surface tension, viscosity, and diffusion coefficient. Notably, near critical points, surface tension and viscosity exhibit distinct scaling relationships with temperature, with viscosity showing much greater sensitivity. Additionally, we found that sequences with high ϕ^{*} may impede the efficient growth of droplets. Our findings provide a framework for understanding sequence-dependent material properties and offer valuable insights into designing biomolecular condensates with tailored stability and dynamic functionality.