Phosphorylation Toggles the SARS-CoV-2 Nucleocapsid Protein Between Two Membrane-Associated Condensate States.

The SARS-CoV-2 Nucleocapsid protein (N) performs several functions during the viral lifecycle, including transcription regulation and viral genome encapsulation. We hypothesized that N toggles between these functions via phosphorylation-induced conformational change, thereby altering N interactions with membranes and RNA. We found that phosphorylation changes how biomolecular condensates composed of N and RNA interact with membranes: phosphorylated N (pN) condensates form thin films, while condensates with unmodified N are engulfed.

Controlled and orthogonal partitioning of large particles into biomolecular condensates.

Biomolecular condensates arising from liquid-liquid phase separation contribute to diverse cellular processes, such as gene expression. Partitioning of client molecules into condensates is critical to regulating the composition and function of condensates. Previous studies suggest that client size limits partitioning, with dextrans >5 nm excluded from condensates.

Expanding the molecular language of protein liquid-liquid phase separation.

Understanding the relationship between a polypeptide sequence and its phase separation has important implications for analysing cellular function, treating disease and designing novel biomaterials. Several sequence features have been identified as drivers for protein liquid-liquid phase separation (LLPS), schematized as a 'molecular grammar' for LLPS. Here we further probe how sequence modulates phase separation and the material properties of the resulting condensates, targeting sequence features previously overlooked in the literature.

Dual drug-loaded biodegradable Janus particles for simultaneous co-delivery of hydrophobic and hydrophilic compounds.

Bicompartmental Janus particles have many advantages in drug delivery, including co-delivery of two compounds with varying solubilities, differential release kinetics, and two surfaces available for targeting ligands. We present a novel strategy using the double emulsion method for the coencapsulation and staggered release of a hydrophobic and hydrophilic drug from anisotropic PLGA/PCL Janus particles, as well as a UV detection method to measure the release of two different compounds from Janus particles. Curcumin and quercetin were chosen as the model hydrophobic compounds for drug loading studies, while acetaminophen (APAP) and naproxen were chosen as the model hydrophilic–hydrophobic drug pair for encapsulation methods and drug loading.