Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Membrane Interactions of Virus-like Mesoporous Silica Nanoparticles

Häffner, Sara Malekkhaiat ; Parra-Ortiz, Elisa ; Browning, Kathryn L. ; Jørgensen, Elin ; Skoda, Maximilian W.A. ; Montis, Costanza ; Li, Xiaomin ; Berti, Debora ; Zhao, Dongyuan and Malmsten, Martin LU (2021) In ACS Nano 15(4). p.6787-6800
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antimicrobial peptides, bacteria killing, inorganic nanoparticles, membrane disruption, nanoparticle topography, spiky structure
in
ACS Nano
volume
15
issue
4
pages
14 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • scopus:85103752451
  • pmid:33724786
ISSN
1936-0851
DOI
10.1021/acsnano.0c10378
language
English
LU publication?
yes
id
a4a064c9-7e4c-4c9f-967e-327faf6e2607
date added to LUP
2021-04-20 08:52:56
date last changed
2024-06-16 12:37:24
@article{a4a064c9-7e4c-4c9f-967e-327faf6e2607,
  abstract     = {{<p>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. </p>}},
  author       = {{Häffner, Sara Malekkhaiat and Parra-Ortiz, Elisa and Browning, Kathryn L. and Jørgensen, Elin and Skoda, Maximilian W.A. and Montis, Costanza and Li, Xiaomin and Berti, Debora and Zhao, Dongyuan and Malmsten, Martin}},
  issn         = {{1936-0851}},
  keywords     = {{antimicrobial peptides; bacteria killing; inorganic nanoparticles; membrane disruption; nanoparticle topography; spiky structure}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  pages        = {{6787--6800}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{ACS Nano}},
  title        = {{Membrane Interactions of Virus-like Mesoporous Silica Nanoparticles}},
  url          = {{http://dx.doi.org/10.1021/acsnano.0c10378}},
  doi          = {{10.1021/acsnano.0c10378}},
  volume       = {{15}},
  year         = {{2021}},
}