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Membrane Interactions of Virus-like Mesoporous Silica Nanoparticles

Häffner, Sara Malekkhaiat (author)
University of Copenhagen
Parra-Ortiz, Elisa (author)
University of Copenhagen
Browning, Kathryn L. (author)
University of Copenhagen
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Jørgensen, Elin (author)
University of Copenhagen
Skoda, Maximilian W.A. (author)
ISIS Neutron and Muon Source
Montis, Costanza (author)
University of Florence
Li, Xiaomin (author)
Fudan University
Berti, Debora (author)
University of Florence
Zhao, Dongyuan (author)
Fudan University
Malmsten, Martin (author)
Lund University,Lunds universitet,Fysikalisk kemi,Enheten för fysikalisk och teoretisk kemi,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Physical Chemistry,Physical and theoretical chemistry,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,University of Copenhagen
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 (creator_code:org_t)
2021-03-16
2021
English 14 s.
In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 15:4, s. 6787-6800
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

TEKNIK OCH TEKNOLOGIER  -- Nanoteknik -- Nanoteknik (hsv//swe)
ENGINEERING AND TECHNOLOGY  -- Nano-technology -- Nano-technology (hsv//eng)
NATURVETENSKAP  -- Kemi -- Fysikalisk kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences -- Physical Chemistry (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Keyword

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

Publication and Content Type

art (subject category)
ref (subject category)

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