Interaction study between maltose-modified PPI dendrimers and lipidic model membranes

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Biophysics

Background:

• Poly(propylene imine) (PPI) dendrimers are versatile macromolecules with tunable surface properties.
• Glycodendrimers, modified with carbohydrates like maltose, offer potential for targeted biological interactions.
• Liposomes serve as model biological membranes to study drug delivery and biomaterial interactions.

Purpose of the Study:

• To investigate the interactions between maltose-modified PPI dendrimers (glycodendrimers) and model liposomes.
• To evaluate the influence of glycodendrimer modification (open shell vs. dense shell) and liposome charge (neutral vs. anionic) on membrane properties.
• To elucidate the underlying mechanisms driving glycodendrimer-liposome interactions.

Main Methods:

• Preparation of fourth-generation (G4) PPI dendrimers with partial (OS) or complete (DS) maltose modification.
• Utilized dimyristoylphosphatidylcholine (DMPC) and DMPC/dimyristoylphosphatidylglycerol (DMPC/DMPG) liposomes (100nm diameter) as model membranes.
• Employed fluorescence spectroscopy, differential scanning calorimetry (DSC), and pulsed-field gradient NMR to analyze membrane fluidity, thermodynamic changes, and diffusion coefficients.

Main Results:

• Both OS and DS glycodendrimers interacted with DMPC and DMPC/DMPG liposomes, affecting membrane fluidity.
• Dense shell (DS) glycodendrimers induced more significant changes in membrane fluidity than open shell (OS) variants.
• Anionic DMPC/DMPG liposomes exhibited increased bilayer rigidity compared to neutral DMPC liposomes; higher OS glycodendrimer concentrations led to aggregation of anionic liposomes.
• Sodium chloride (NaCl) diminished the interaction strength between glycodendrimers and liposomes.
• NMR data suggested that hydrogen bonding, in addition to electrostatic forces, plays a crucial role in the interaction between maltose shells and liposome surfaces.

Conclusions:

• Maltose-modified PPI dendrimers effectively interact with both neutral and anionic model membranes.
• The degree of surface modification and liposome charge influence the extent of interaction and membrane perturbation.
• Hydrogen bonding is a significant interaction mechanism, particularly for OS glycodendrimers, highlighting the importance of the maltose shell in mediating these associations.