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Interazioni lipidi-proteine per l’assemblamento di nanostrutture funzionali Dipartimento di Medicina Sperimentale (DMS) Massimo Masserini Francesca Re Silvia Sesana Alessandra Bulbarelli Cristina Bianchi.
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Interazioni lipidi-proteine per l’assemblamento di nanostrutture funzionali Dipartimento di Medicina Sperimentale (DMS) Massimo Masserini Francesca Re Silvia Sesana Alessandra Bulbarelli Cristina Bianchi
RATIONALE: lipid domains are specialized zones of the membrane enriched in peculiar lipids (glycolipids, sphingomyelin, cholesterol). Selected proteins (e.g. containing a palmitoyl- or a glycosyl- phosphatidylinositol anchor or an highly hydrophobic TMD) are recruited within rafts due to lipid-protein interactions 10-20nm 100 nm A set of selected molecules can be chemically derivatized ( e.g. by palmitoylation) and targeted to rafts in order to realize a nano-scale cassette accomplishing a biological task (e.g. therapy) SMALL UNILAMELLAR VESICLES extrusion under dipersion of lipids in N2 pressure water
Differential Scanning Calorimetry (DSC) • DSC is used to monitor thermotropic properties: transition temperature (Tm) and enthalpy (H) of gel-liquid transition • Information about the existence of lipid domains • Interactions of proteins with domains
66% 33% 67% 34% b5ext interacts with Phosphatidylserine domains (Masserini et al.PNAS , 2006) Phosphatidylcholine Phosphatidylserine 60% 40% Phosphatidylcholine enriched Phosphatidylserine enriched
Esempio: rimozione in circolo di molecole di adesione presenti sull’endotelio, sui leucociti e su cellule tumorali, e coinvolte in processi infiammatori e nella metastatizzazione dei tumori PI-PLC CELLULA N SMALL UNILAMELLAR VESICLE Anticorpo Molecole di adesione