Biomolecular condensates as potential carriers of pharmacological molecules

The project explores the potential of biomolecular condensates, formed by GRASP proteins, as carriers for pharmacological molecules, using gallic acid (GA) as a model. These condensates are dynamic, membrane-free compartments formed via phase separation (PS) through multivalent protein interactions. GRASP proteins, located in the Golgi complex, can form condensates under stress, recruiting molecules. GA is a natural polyphenol with antioxidant, anti-inflammatory, and metal-chelating properties. It modulates tau protein PS, linked to pathological aggregates in neurodegenerative diseases. To achieve the central objective, we propose to investigate the interaction between gallic acid and cell membrane models as a first step towards investigating its interaction with GRASP condensates. Preliminary differential scanning calorimetry (DSC) experiments demonstrated that gallic acid slightly altered the phase transition temperature of DMPC. We also performed absorbance experiments, which showed that gallic acid has good absorbance at wavelengths between 270 and 280 nm. This will guide the selection of markers for future fluorescence microscopy and spectroscopy experiments to investigate the interaction between gallic acid and cell membrane models or condensates. We also propose to investigate the ability of GRASP condensates to recruit GA, utilizing bright-field and fluorescence microscopy. Finally, we will investigate the interaction between condensates containing GA and cell membrane models, following a similar strategy to the one mentioned for GA alone. Expected results include elucidating the mechanisms governing the interaction between biomolecular condensates and GA. The identification of specific interactions will allow understanding how properties like charge and hydrophobicity influence GA's partitioning and stabilization. The investigation also seeks to reveal whether GRASP condensates act as effective platforms for encapsulating and potentially releasing bioactive compounds. Positive results would open the possibility of utilizing condensates as bio-inspired systems for intracellular drug delivery.