Membrane interactions of antimicrobial peptide-loaded microgels.
Nordström. Randi R; Browning. Kathryn L KL; Parra-Ortiz. Elisa E; Damgaard. Liv Sofia Elinor LSE; Häffner. Sara Malekkhaiat SM; Maestro. Armando A; Campbell. Richard A RA; Cooper. Joshaniel F K JFK; Malmsten. Martin M
Key Findings
- Free LL‑37 binds to the outer leaflet of lipid membranes at low concentrations and creates defects in both leaflets at higher concentrations.
- Microgel‑loaded LL‑37 shows the same membrane‑binding pattern, but the effect is delayed because the peptide is released slowly.
- The microgel particles themselves have minimal direct interaction with membranes, indicating that any observed effects are due to the released peptide.
Practical Outcomes
- For DIY health enthusiasts, this work suggests that using LL‑37 in a slow‑release carrier (like a microgel) could temper its membrane‑disrupting activity, potentially reducing irritation when applied topically. However, the study does not provide dosing guidelines or clear performance benefits, so it’s mainly of interest for those experimenting with peptide delivery systems rather than immediate health protocols.
Summary
The study looked at how the antimicrobial peptide LL‑37 interacts with cell‑like membranes when it’s delivered free versus when it’s packed inside tiny gel particles (microgels). It found that the peptide itself does the heavy lifting – it binds to and disrupts membranes, especially at higher concentrations – while the gel particles barely stick to the membrane. Loading LL‑37 into the microgels slows its release, which in turn slows the peptide’s ability to insert into the membrane and form its usual helix shape.
Abstract
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.
Study Information
pubmed
2019
2019-12-09T00:00:00.000Z
10.1016/j.jcis.2019.12.022
21
52