2 research outputs found
Biophysical Properties and Supramolecular Structure of Self-Assembled Liposome/ε-Peptide/DNA Nanoparticles: Correlation with Gene Delivery
Using solid-phase synthesis, lysine can be oligomerized
by a reaction
of the peptide carboxylate with the ε-amino group to produce
nontoxic, biodegradable cationic peptides, ε-oligo(l-lysines). Here α-substituted derivatives of such ε-oligo(l-lysines) containing arginine and histidine in the side chain
were tested as vectors for in vitro gene delivery. Combination of
ε-oligolysines with the cationic lipid DOTAP and plasmid DNA
resulted in transfection efficiency exceeding that of DOTAP alone,
without significant increase in cytotoxicity. Synchrotron small-angle
X-ray scattering studies revealed self-assembly of the DOTAP, ε-oligolysines,
and DNA to ordered lamellar complexes. High transfection efficiency
of the nanoparticles correlates with increase in zeta potential above
+20 mV and requires particle size to be below 500 nm. The synergistic
effect of branched ε-oligolysines and DOTAP in gene delivery
can be explained by the increase in surface charge and by the supramolecular
structure of the DOTAP/ε-oligolysine/DNA nanoparticles
Supramolecular Organization in Self-Assembly of Chromatin and Cationic Lipid Bilayers is Controlled by Membrane Charge Density
In this work we have investigated
the structures of aggregates
formed in model systems of dilute aqueous mixtures of “model
chromatin” consisting of either recombinant nucleosome core
particles (NCPs) or nucleosome arrays consisting of 12 NCPs connected
with 30 bp linker DNA, and liposomes made from different mixtures
of cationic and zwitterionic lipids, 1,2-dioleoyl-3-trimethylammonium-propane
chloride salt (DOTAP) and 1,2-dioleoyl-<i>sn</i>-glycero-3-phosphocholine
(DOPC). The aggregates formed were characterized using different optical
microscopy methods and small-angle X-ray scattering (SAXS), and the
results are discussed in terms of the competing intermolecular interactions
among the components. For a majority of the samples, the presence
of lamellar structures could be identified. In samples with high fractions
of DOTAP in the liposomes, well-defined lamellar structures very similar
to those formed by the corresponding lipid mixtures and DNA alone
(i.e., without histone proteins) were observed; in these aggregates,
the histones are expelled from the model chromatin. The findings suggest
that, with liposomes containing large fractions of cationic lipid,
the dominating driving force for aggregation is the increase in translational
entropy from the release of counterions, whereas with lower fractions
of the cationic lipid, the entropy of mixing of the lipids within
the bilayers results in a decreased DNA–lipid attraction