BPS2026 – Interplay between mesh reconfigurability and molecular shape memory governs the viscoelasticity of biomolecular condensates

Biomolecular condensates are membraneless organelles that maintain structural coherence and compartmentalize biological function in cells. Formed by the phase separation of biomolecules, condensates possess a wide range of mechanical responses that have important biological functions. However, how these properties are encoded in the chemistries of their constituents—such as proteins with prion-like low-complexity domains (LCDs)—are not well understood. Here, we employ molecular dynamics simulations to connect measurable condensate viscoelastic stress response to the degree of architectural heterogeneity and dynamic reconfigurability of associative networks formed by intrinsically disordered proteins (IDPs). Using a residue-resolution coarse-grained model, we characterize biologically relevant and synthetic condensates, demonstrating that their temperature sensitivity of elasticity is sequence-dependent and modeled by exponential scaling laws. We also interrogate condensate mesh heterogeneity via entanglement spacing, finding that entropy-driven structural heterogeneity and reduced IDP hydrophobicity favor condensate elasticity. Furthermore, we construct graph-theoretical representations of condensates and find that interaction network topologies with an abundance of redundant node pathways translates to more load-bearing paths for mechanical stress storage. Moreover, we discover that elastic coupling of IDPs within condensates emerges when single-molecule shape memory timescales approach meshwork reconfiguration timescales. This interplay of characteristic timescales for molecular and microstructural processes dictates how restoring elastic forces propagate and are stored across IDP networks. Taken together, our work provides a conceptual framework in which condensates act as stress-responsive biomaterials, helping illuminate how cells exploit condensate mechanics to sense and regulate their internal environment and opening avenues for the design of condensates with programmable material properties.