Polyamidoamine (PAMAM) dendrimers are hyper-branched, nanosized polymers with promising
biomedical applications as nanocarriers in targeted drug delivery and gene therapy.
For the development of safe dendrimer-based biomedical applications it is necessary
to gain an understanding of the detailed mechanism of the interactions of both cationic
and anionic dendrimers with cell membranes. To characterize dendrimer membrane interactions
we applied solid-supported lipid bilayers as biomembrane models and utilized infrared
visible sum-frequency vibrational spectroscopy to independently probe the interactions
of cationic G5-NH2 and anionic G4.5-COONa dendrimers with the two leaflets of the
lipid bilayers. Interaction with both dendrimers led to changes in the interfacial
water structure and charge density as evidenced by the changes in the OH band intensities
in the sum-frequency spectra of the bilayers. Interaction with the G5-NH2 dendrimer
also led to a unique inversion of the sign of the OH-stretch amplitudes, in addition
to a decrease in their absolute values. We suggest that the positively charged amino
groups on the G5-NH2 dendrimer surface bind to the negatively charged bilayer, while
uncompensated positive charges not involved in the binding cause a reversal of the
electric field and thus an opposite orientation of the interfacial water molecules.
More subtle but nonetheless significant changes were seen in the relative magnitudes
of the CH amplitudes. The methyl antisymmetric to symmetric stretch amplitude ratios
are altered, implying changes in the tilt angles of the phospholipid alkyl chains.
The conformational order of the phospholipid alkyl chains of both leaflets is also
influenced by the G5-NH2 dendrimer while G4.5-COONa has no effect on the alkyl chain