16 February 2024 | Ibraheem Alshareedah, Anurag Singh, Sean Yang, Vysakh Ramachandran, Alexander Quinn, Davit A. Potoyan, Priya R. Banerjee
Biomolecular condensates exhibit viscoelastic properties influenced by intermolecular interactions and chain length. This study combines microrheology and molecular simulations to investigate the physical determinants of condensate dynamics. The viscoelastic behavior of condensates is governed by network relaxation times and flow activation energy, which is independent of chain length but depends on intermolecular interactions. The energy barrier for network reconfiguration, termed flow activation energy, is directly linked to the dissociation of sticker motifs from DNA chains. The results show that flow activation energy is a unique indicator of multivalent intermolecular interactions in condensates. Chain length variations primarily affect viscoelasticity without altering flow activation energy. Polypeptide diffusion in the dense phase is inversely correlated with flow activation energy and is not significantly affected by ssDNA length. The study demonstrates that biomolecular diffusion in condensates is governed by a reaction-limited diffusion mechanism. The findings highlight the importance of intermolecular interactions and chain length in determining the viscoelastic and transport properties of biomolecular condensates. The results suggest that the flow activation energy can be used to quantify the strength of intermolecular interactions in condensates. The study also shows that the viscoelastic properties of condensates are sensitive to sequence and chain length of component biomolecules, ionic strength, and pH. The results indicate that the regulation of macromolecule mobility within condensates can be achieved through reaction-dominant transport mechanisms or assisted transport. The study provides insights into the altered viscoelastic behavior of condensates upon sequence and length variation of constituent biopolymers. The findings have implications for understanding the regulation of macromolecular diffusion within condensates and for engineering biomolecular condensates with desired material and transport properties.Biomolecular condensates exhibit viscoelastic properties influenced by intermolecular interactions and chain length. This study combines microrheology and molecular simulations to investigate the physical determinants of condensate dynamics. The viscoelastic behavior of condensates is governed by network relaxation times and flow activation energy, which is independent of chain length but depends on intermolecular interactions. The energy barrier for network reconfiguration, termed flow activation energy, is directly linked to the dissociation of sticker motifs from DNA chains. The results show that flow activation energy is a unique indicator of multivalent intermolecular interactions in condensates. Chain length variations primarily affect viscoelasticity without altering flow activation energy. Polypeptide diffusion in the dense phase is inversely correlated with flow activation energy and is not significantly affected by ssDNA length. The study demonstrates that biomolecular diffusion in condensates is governed by a reaction-limited diffusion mechanism. The findings highlight the importance of intermolecular interactions and chain length in determining the viscoelastic and transport properties of biomolecular condensates. The results suggest that the flow activation energy can be used to quantify the strength of intermolecular interactions in condensates. The study also shows that the viscoelastic properties of condensates are sensitive to sequence and chain length of component biomolecules, ionic strength, and pH. The results indicate that the regulation of macromolecule mobility within condensates can be achieved through reaction-dominant transport mechanisms or assisted transport. The study provides insights into the altered viscoelastic behavior of condensates upon sequence and length variation of constituent biopolymers. The findings have implications for understanding the regulation of macromolecular diffusion within condensates and for engineering biomolecular condensates with desired material and transport properties.