Sequence-Dependent Material Properties of Biomolecular Condensates. Academic Article uri icon


  • Material properties of phase-separated biomolecular assemblies, enriched with disordered proteins, dictate their ability to participate in many cellular functions. Despite the significant effort dedicated to understanding how the sequence of the disordered protein drives its phase separation to form condensates, little is known about the sequence determinants of condensate material properties. Here, we decipher these relationships for charged disordered proteins using model sequences comprised of glutamic acid and lysine residues as well as naturally occurring sequences of LAF1's RGG domain and DDX4's N-terminal domain. We do so by delineating how the arrangement of oppositely charged residues within these sequences influences the dynamical, rheological, and interfacial properties of the condensed phase. Interestingly, we find that the material properties of both the model and natural proteins respond similarly to the segregation of charges, despite their very different sequence compositions. Condensates of the highly charge- segregated sequences exhibit slower dynamics than the uniformly charge-patterned sequences, because of their comparatively long-lived molecular contacts between oppositely charged residues. Surprisingly, the molecular interactions within the condensate are highly similar to those within a single-chain for all sequences. Consequently, the condensate material properties of charged disordered proteins are strongly correlated with their dense-phase contact dynamics and their single-chain structural properties. Our findings demonstrate the potential to harness the sequence characteristics of disordered proteins for engineering the material properties of functional condensates, with insights from the dilute-phase properties.

published proceedings

  • bioRxiv

altmetric score

  • 8.25

author list (cited authors)

  • Devarajan, D. S., Wang, J., Nikoubashman, A., Kim, Y. C., & Mittal, J.

citation count

  • 0

complete list of authors

  • Devarajan, Dinesh Sundaravadivelu||Wang, Jiahui||Nikoubashman, Arash||Kim, Young C||Mittal, Jeetain

publication date

  • May 2023