
Diblock elastin-like polypeptides undergo microphase separation, producing condensates with an interfacial environment that features a blend of hydrophobic and hydrophilic regions, which is crucial for their stability and organization.


coremsg

The phase separation of intrinsically disordered proteins is emerging as an important mechanism for cellular organization. However, efforts to connect protein sequences to the physical properties of condensates, i.e., the molecular grammar, are hampered by a lack of effective approaches for probing high-resolution structural details. Using a combination of multiscale simulations and fluorescence lifetime imaging microscopy experiments, we systematically explored a series of systems consisting of diblock elastin-like polypeptides (ELP). The simulations succeeded in reproducing the variation of condensate stability upon amino acid substitution and revealed different microenvironments within a single condensate, which we verified with environmentally sensitive fluorophores. The interspersion of hydrophilic and hydrophobic residues and a lack of secondary structure formation result in an interfacial environment, which explains both the strong correlation between ELP condensate stability and interfacial hydrophobicity scales, as well as the prevalence of protein-water hydrogen bonds. Our study uncovers new mechanisms for condensate stability and organization that may be broadly applicable.

### Competing Interest Statement

The authors have declared no competing interest.

Microphase Separation Produces Interfacial Environment within Diblock Biomolecular Condensates

multiscale-simulations-and-experiments-reveal-interfacial-microenvironments-within-biological-condensates-formed-by-elastin-like-polypeptides


Multiscale Simulations and Experiments Reveal Interfacial Microenvironments within Biological Condensates Formed by Elastin-like Polypeptides
