In the present study,
we investigated lipid membrane interactions
of silica nanoparticles as carriers for the antimicrobial peptide
LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES).
In doing so, smooth mesoporous nanoparticles were compared to virus-like
mesoporous nanoparticles, characterized by a “spiky”
external surface, as well as to nonporous silica nanoparticles. For
this, we employed a combination of neutron reflectometry, ellipsometry,
dynamic light scattering, and ζ-potential measurements for studies
of bacteria-mimicking bilayers formed by palmitoyloleoylphosphatidylcholine/palmitoyloleoylphosphatidylglycerol.
The results show that nanoparticle topography strongly influences
membrane binding and destabilization. We found that virus-like particles
are able to destabilize such lipid membranes, whereas the corresponding
smooth silica nanoparticles are not. This effect of particle spikes
becomes further accentuated after loading of such particles with LL-37.
Thus, peptide-loaded virus-like nanoparticles displayed more pronounced
membrane disruption than either peptide-loaded smooth nanoparticles
or free LL-37. The structural basis of this was clarified by neutron
reflectometry, demonstrating that the virus-like nanoparticles induce
trans-membrane defects and promote incorporation of LL-37 throughout
both bilayer leaflets. The relevance of such effects of particle spikes
for bacterial membrane rupture was further demonstrated by confocal
microscopy and live/dead assays on Escherichia coli bacteria. Taken together, these findings demonstrate that topography
influences the interaction of nanoparticles with bacteria-mimicking
lipid bilayers, both in the absence and presence of antimicrobial
peptides, as well as with bacteria. The results also identify virus-like
mesoporous nanoparticles as being of interest in the design of nanoparticles
as delivery systems for antimicrobial peptides.