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).
10-20 nm
100 nm
SMALL UNILAMELLAR VESICLES
Selected proteins (e.g. containing
a palmitoyl- or a glycosylphosphatidylinositol anchor or an
highly hydrophobic TMD) are
recruited within rafts due to
lipid-protein interactions
A set of selected molecules can be
chemically derivatized ( e.g. by
palmitoylation) and targeted to
rafts in order to realize a nanoscale cassette accomplishing a
biological task (e.g. therapy)
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
QuickTime™ and a
Cinepak decompressor
are needed to see this picture.
• Information about the
existence
of
lipid
domains
• Interactions of proteins
with domains
b5ext interacts with Phosphatidylserine domains
(Masserini et al. PNAS , 2006)
Phosphatidylcholine
Phosphatidylserine
60%
66%
40%
Phosphatidylcholine
enriched
33%
Phosphatidylserine
enriched
67%
34%
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