Membrane interactions of antimicrobial peptide-loaded microgels
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Membrane interactions of antimicrobial peptide-loaded microgels. / Nordström, Randi; Browning, Kathryn L; Parra-Ortiz, Elisa; Damgaard, Liv Sofia Elinor; Häffner, Sara Malekkhaiat; Maestro, Armando; Campbell, Richard A; Cooper, Joshaniel F K; Malmsten, Martin.
In: Journal of Colloid and Interface Science, Vol. 562, 2020, p. 322-332.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Membrane interactions of antimicrobial peptide-loaded microgels
AU - Nordström, Randi
AU - Browning, Kathryn L
AU - Parra-Ortiz, Elisa
AU - Damgaard, Liv Sofia Elinor
AU - Häffner, Sara Malekkhaiat
AU - Maestro, Armando
AU - Campbell, Richard A
AU - Cooper, Joshaniel F K
AU - Malmsten, Martin
N1 - Copyright © 2019 Elsevier Inc. All rights reserved.
PY - 2020
Y1 - 2020
N2 - In the present study, lipid membrane interactions of anionic poly(ethyl acrylate-co-methacrylic acid) (MAA) microgels as carriers for the cationic antimicrobial peptide LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) were investigated. In doing so, neutron reflectometry (NR), Fourier-transform infrared spectroscopy with attenuated total reflection (FTIR-ATR), zeta potential, ellipsometry, and circular dichroism spectroscopy (CD) experiments were employed to investigate the relative importance of membrane interactions of peptide-loaded microgel particles and of released peptide. For the free peptide, NR results showed membrane binding occurring preferentially in the tail region in a concentration-dependent manner. At low peptide concentration (0.3 μM) only peptide insertion in the outer leaflet was seen, however, pronounced membrane defects and peptide present in both leaflets was observed at higher peptide concentration (5.0 μM). LL-37 loaded into MAA microgels qualitatively mirrored these effects regarding both peptide localization within the membrane and concentration-dependent defect formation. In addition, very limited membrane binding of microgel particles was observed, in agreement with FTIR-ATR and liposome leakage results. FTIR-ATR showed LL-37 to undergo α-helix formation on membrane insertion, also supported by CD results, the kinetics of which was substantially reduced for microgel-loaded LL-37 due to sustained peptide release. Together, these findings demonstrate that membrane interactions for microgel-loaded LL-37 are dominated by released peptide, but also that slow release of microgel-loaded LL-37 translates into kinetic effects on peptide-membrane interactions, relating to both peptide localization within the bilayer, and to bilayer structure.
AB - In the present study, lipid membrane interactions of anionic poly(ethyl acrylate-co-methacrylic acid) (MAA) microgels as carriers for the cationic antimicrobial peptide LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) were investigated. In doing so, neutron reflectometry (NR), Fourier-transform infrared spectroscopy with attenuated total reflection (FTIR-ATR), zeta potential, ellipsometry, and circular dichroism spectroscopy (CD) experiments were employed to investigate the relative importance of membrane interactions of peptide-loaded microgel particles and of released peptide. For the free peptide, NR results showed membrane binding occurring preferentially in the tail region in a concentration-dependent manner. At low peptide concentration (0.3 μM) only peptide insertion in the outer leaflet was seen, however, pronounced membrane defects and peptide present in both leaflets was observed at higher peptide concentration (5.0 μM). LL-37 loaded into MAA microgels qualitatively mirrored these effects regarding both peptide localization within the membrane and concentration-dependent defect formation. In addition, very limited membrane binding of microgel particles was observed, in agreement with FTIR-ATR and liposome leakage results. FTIR-ATR showed LL-37 to undergo α-helix formation on membrane insertion, also supported by CD results, the kinetics of which was substantially reduced for microgel-loaded LL-37 due to sustained peptide release. Together, these findings demonstrate that membrane interactions for microgel-loaded LL-37 are dominated by released peptide, but also that slow release of microgel-loaded LL-37 translates into kinetic effects on peptide-membrane interactions, relating to both peptide localization within the bilayer, and to bilayer structure.
U2 - 10.1016/j.jcis.2019.12.022
DO - 10.1016/j.jcis.2019.12.022
M3 - Journal article
C2 - 31855795
VL - 562
SP - 322
EP - 332
JO - Journal of Colloid and Interface Science
JF - Journal of Colloid and Interface Science
SN - 0021-9797
ER -
ID: 239515124