Membrane interactions of virus-like mesoporous silica nanoparticles

Sara Malekkhaiat Häffner, Elisa Parra-Ortiz, Kathryn L. Browning, Elin Jørgensen, Maximilian W.A. Skoda, Costanza Montis, Xiaomin Li, Debora Berti, Dongyuan Zhao, Martin Malmsten

Research output: Contribution to journalArticleResearchpeer-review

52 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6787-6800
Number of pages14
JournalACS Nano
Volume15
Issue number4
DOIs
Publication statusPublished - 27 Apr 2021
Externally publishedYes

Keywords

  • antimicrobial peptides
  • bacteria killing
  • inorganic nanoparticles
  • membrane disruption
  • nanoparticle topography
  • spiky structure

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