Membrane-Based Nanotechnology and Drug Delivery - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 130

removed can be referred to using the word hole or pore. In Chap. 4 we have discussed
the various antimicrobial peptide-induced membrane transport events, such as ion
flowing channels, pores, defects, etc. For details of experimental observations of such
events in supported lipid bilayers (SLBs) induced by nonpeptides the reader may
consult various publications such as [ 15 - 17 ], etc. The above-mentioned complete
loss of lipids is usually a transient phenomenon. Due to the liquid crystalline nature
of the lipid membrane and the presence of strong statistical-mechanical effects on
membrane dynamics, the nearby lipids fill in the gap quickly. In this section we
address the issue of the possible nanoparticle disruption of the membrane, using a
few reference studies.

6.3.2 Membrane Disruption Depends on Size and Structure
of Nanoparticles

In a recent study [ 11 ] polycationic organic nanoparticles were found to disrupt model
biological membranes and living cell membranes. Few nanoscale (

∼

3, 5 and 7 nm)
polymeric scaffolds called polyamidoamine (PAMAM) dendrimers were studied for
their effects on membranes. The degree of membrane disruption is shown to be
related to nanoparticle size and charge, as well as to the lipid phase states (such as
fluid, liquid crystalline, or gel) of the biological membrane (see Chap. 3 ) .
Disruption events in model membranes have been directly imaged using scanning
probe microscopy, whereas disruption events in living cells have been analyzed using
cytosolic enzyme leakage assays, dye diffusion assays, and fluorescence microscopy
as described in the above-mentioned study [ 11 ]. The results presented here (Fig. 6.1 )
suggest that a 20nm diameter hole is created in the supported lipid bilayer (SLB) by
the G7 dendrimer. The relatively smaller G5 dendrimer does not create a hole, but
can still participate in the expansion of the existing nanosize holes and defects in the
bilayer. Here, the main message is that larger size dendrimers can possibly create
larger holes or cause greater membrane disruption. A set of polycationic organic poly-
mers such as poly-L-lysine (PLL), polyethyleneimine (PEI), and dielthylaminoethyl-
dextran (DEAE-dextran) and neutral polymers such as polyethylene glycol (PEG)
and polyvinyl alcohol (PVA) were also investigated for their membrane disruption
in the same studies [ 11 ]. As presented in Fig. 6.2 (panel I), we observe that the
polycationic polymers exhibit substantial membrane disruption behavior, including
nanoscale hole formation. However, the neutral polymers PEG and PVA are not
found to induce membrane disruption. More studies, though, are needed to under-
stand the role of size and charge density of these membrane-disrupting polymers in
their induction of nanosize holes in the membranes. LDH leakage results from both
figures (see Figs. 6.1 and 6.2 ) are consistent with the observed effects.
Identical results of polycationic polymer effects on bilayer disruption were also
reported in an earlier publication [ 16 ]. Holes with 15-40nmdiameters were observed
here to be induced due to polymers, and the hole size was found to be largely reduced