Biomedical Engineering Reference
In-Depth Information
Fig. 6.1 In this figure the dendrimer interactions with biological membranes have been analyzed.
In panel I, the atomic force microscopy (AFM) observation of dimyristoylphosphatidylcholine
(DMPC)-supported lipid bilayers (a,c,e) before and after incubation with b G7-NH 2 , d G5-NH 2 ,
and f G5-Ac PAMAM dendrimers have been presented. Panel II: Space-filling models of chemical
structures of a G7-NH 2 , b G5-NH 2 ,and c G5-Ac PAMAM dendrimers have been presented.
Panel III presents: lactate dehydrogenase (LDH) leakage as a result of cell exposure to PAMAM
dendrimers, showing a size effect of G7-NH 2 and G5-NH 2 on the LDH leakage out of KB and
Rat2 cells after incubation at 37 Cfor3hand b surface group dependence on the LDH leakage at
different temperatures. Note that larger (
8.2 nm) dendrimers (G7-NH 2 ) induce formation of new
nanoscale holes in the bilayers as seen in the AFM images and cause a greater amount of LDH
leakage out of live cells than relatively smaller G5-NH 2 .G5-NH 2 dendrimers do not cause new
hole formation in the lipid bilayers, but instead expand pre-existing defects. In contrast, G5-Ac
dendrimers do not cause hole formation, expansion of pre-existing defects, or LDH leakage out of
live cells. This figure with description has been taken with the publisher's permission from [ 11 ]
as the polymer size becomes smaller. No hole was found to be created by a very
small dendrimer (e.g. G3-amine). Acetamide-terminated G5 dendrimers were also
not found to be creating any holes.
The experimental observations mentioned above and elsewhere indicate the exis-
tence of clear size- and structure-specific effects of polycationic polymers in the
nanoscale membrane disruption mechanism. In all instances, the edges of bilayer
defects proved to be points of highest dendrimer activity. A proposed mechanism for
the removal of lipids by dendrimers involves the formation of transient, nanoscale
dendrimer-filled lipid vesicles, as shown in Fig. 6.3 . By considering the thermo-
dynamics, interaction free energy, and geometry of these self-assembled vesicles, a
model that explains the influence of polymer particle size and surface chemistry on
the interactions with lipid membranes was developed.
Considering interactions between lipid molecules in the vesicles and between
lipid molecules and the specific dendrimer inside the vesicle, one can explain the
energetics of the dendrimer-induced pore formation in the lipid bilayer.
 
Search WWH ::




Custom Search