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Conformational control of antimicrobial peptide amphiphilicity : consequences for boosting membrane interactions and antimicrobial effects of photocatalytic TiO2 nanoparticles

Caselli, Lucrezia LU ; Köhler, Sebastian LU ; Schirone, Davide LU ; Humphreys, Ben LU and Malmsten, Martin LU (2024) In Physical Chemistry Chemical Physics 26(23). p.16529-16539
Abstract

This study reports on the effects of conformationally controlled amphiphilicity of antimicrobial peptides (AMPs) on their ability to coat TiO2 nanoparticles (NPs) and boost the photocatalytic antimicrobial effects of such NPs. For this, TiO2 NPs were combined with AMP EFK17 (EFKRIVQRIKDFLRNLV), displaying a disordered conformation in aqueous solution but helix formation on interaction with bacterial membranes. The membrane-bound helix is amphiphilic, with all polar and charged amino acid residues located at one side and all non-polar and hydrophobic residues on the other. In contrast, the d-enantiomer variant EFK17-d (E(dF)KR(dI)VQR(dI)KD(dF)LRNLV) is unable to form the amphiphilic helix on bacterial membrane... (More)

This study reports on the effects of conformationally controlled amphiphilicity of antimicrobial peptides (AMPs) on their ability to coat TiO2 nanoparticles (NPs) and boost the photocatalytic antimicrobial effects of such NPs. For this, TiO2 NPs were combined with AMP EFK17 (EFKRIVQRIKDFLRNLV), displaying a disordered conformation in aqueous solution but helix formation on interaction with bacterial membranes. The membrane-bound helix is amphiphilic, with all polar and charged amino acid residues located at one side and all non-polar and hydrophobic residues on the other. In contrast, the d-enantiomer variant EFK17-d (E(dF)KR(dI)VQR(dI)KD(dF)LRNLV) is unable to form the amphiphilic helix on bacterial membrane interaction, whereas the W-residues in EFK17-W (EWKRWVQRWKDFLRNLV) boost hydrophobic interactions of the amphiphilic helix. Circular dichroism results showed the effects displayed for the free peptide, to also be present for peptide-coated TiO2 NPs, causing peptide binding to decrease in the order EFK17-W > EFK17 > EFK17-d. Notably, the formation of reactive oxygen species (ROS) by the TiO2 NPs was essentially unaffected by the presence of peptide coating, for all the peptides investigated, and the coatings stabilized over hours of UV exposure. Photocatalytic membrane degradation from TiO2 NPs coated with EFK17-W and EFK17 was promoted for bacteria-like model bilayers containing anionic phosphatidylglycerol but suppressed in mammalian-like bilayers formed by zwitterionic phosphatidylcholine and cholesterol. Structural aspects of these effects were further investigated by neutron reflectometry with clear variations observed between the bacteria- and mammalian-like model bilayers for the three peptides. Mirroring these results in bacteria-like model membranes, combining TiO2 NPs with EFK17-W and EFK17, but not with non-adsorbing EFK17-d, resulted in boosted antimicrobial effects of the resulting cationic composite NPs already in darkness, effects enhanced further on UV illumination.

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; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Physical Chemistry Chemical Physics
volume
26
issue
23
pages
11 pages
publisher
Royal Society of Chemistry
external identifiers
  • pmid:38828872
  • scopus:85195043591
ISSN
1463-9076
DOI
10.1039/d4cp01724b
language
English
LU publication?
yes
id
91738662-db9f-4a7f-bb19-d6ef92cee05e
date added to LUP
2024-08-20 12:34:32
date last changed
2024-08-26 12:29:30
@article{91738662-db9f-4a7f-bb19-d6ef92cee05e,
  abstract     = {{<p>This study reports on the effects of conformationally controlled amphiphilicity of antimicrobial peptides (AMPs) on their ability to coat TiO<sub>2</sub> nanoparticles (NPs) and boost the photocatalytic antimicrobial effects of such NPs. For this, TiO<sub>2</sub> NPs were combined with AMP EFK17 (EFKRIVQRIKDFLRNLV), displaying a disordered conformation in aqueous solution but helix formation on interaction with bacterial membranes. The membrane-bound helix is amphiphilic, with all polar and charged amino acid residues located at one side and all non-polar and hydrophobic residues on the other. In contrast, the d-enantiomer variant EFK17-d (E(dF)KR(dI)VQR(dI)KD(dF)LRNLV) is unable to form the amphiphilic helix on bacterial membrane interaction, whereas the W-residues in EFK17-W (EWKRWVQRWKDFLRNLV) boost hydrophobic interactions of the amphiphilic helix. Circular dichroism results showed the effects displayed for the free peptide, to also be present for peptide-coated TiO<sub>2</sub> NPs, causing peptide binding to decrease in the order EFK17-W &gt; EFK17 &gt; EFK17-d. Notably, the formation of reactive oxygen species (ROS) by the TiO<sub>2</sub> NPs was essentially unaffected by the presence of peptide coating, for all the peptides investigated, and the coatings stabilized over hours of UV exposure. Photocatalytic membrane degradation from TiO<sub>2</sub> NPs coated with EFK17-W and EFK17 was promoted for bacteria-like model bilayers containing anionic phosphatidylglycerol but suppressed in mammalian-like bilayers formed by zwitterionic phosphatidylcholine and cholesterol. Structural aspects of these effects were further investigated by neutron reflectometry with clear variations observed between the bacteria- and mammalian-like model bilayers for the three peptides. Mirroring these results in bacteria-like model membranes, combining TiO<sub>2</sub> NPs with EFK17-W and EFK17, but not with non-adsorbing EFK17-d, resulted in boosted antimicrobial effects of the resulting cationic composite NPs already in darkness, effects enhanced further on UV illumination.</p>}},
  author       = {{Caselli, Lucrezia and Köhler, Sebastian and Schirone, Davide and Humphreys, Ben and Malmsten, Martin}},
  issn         = {{1463-9076}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{23}},
  pages        = {{16529--16539}},
  publisher    = {{Royal Society of Chemistry}},
  series       = {{Physical Chemistry Chemical Physics}},
  title        = {{Conformational control of antimicrobial peptide amphiphilicity : consequences for boosting membrane interactions and antimicrobial effects of photocatalytic TiO<sub>2</sub> nanoparticles}},
  url          = {{http://dx.doi.org/10.1039/d4cp01724b}},
  doi          = {{10.1039/d4cp01724b}},
  volume       = {{26}},
  year         = {{2024}},
}