Membrane interactions of antimicrobial peptide-loaded microgels
Randi Nordström1, Kathryn L Browning2, Elisa Parra-Ortiz3
1Department of Pharmacy, Uppsala University, SE-75123 Uppsala, Sweden.
Journal of Colloid and Interface Science
|December 20, 2019
Summary
Anionic poly(ethyl acrylate-co-methacrylic acid) (MAA) microgels carrying the antimicrobial peptide LL-37 were studied for their lipid membrane interactions. The findings show that released LL-37, not the microgel particles, primarily interacts with membranes, influencing their structure and peptide localization.
Area of Science:
- Biomaterials Science
- Membrane Biophysics
- Antimicrobial Peptide Research
Background:
- Antimicrobial peptides (AMPs) are crucial in innate immunity, but their therapeutic use is limited by stability and delivery challenges.
- Microgels offer a promising platform for controlled delivery of therapeutic agents like AMPs.
- Understanding the interaction of AMP-loaded carriers with biological membranes is essential for effective drug design.
Purpose of the Study:
- To investigate the lipid membrane interactions of anionic poly(ethyl acrylate-co-methacrylic acid) (MAA) microgels loaded with the antimicrobial peptide LL-37.
- To determine the relative contributions of microgel particles and released LL-37 to membrane disruption.
- To elucidate the effect of sustained LL-37 release from microgels on its membrane interaction kinetics and mechanism.
Main Methods:
- Neutron reflectometry (NR) to probe peptide localization and membrane structure.
- Fourier-transform infrared spectroscopy with attenuated total reflection (FTIR-ATR) to assess peptide secondary structure changes.
- Circular dichroism (CD) spectroscopy to confirm peptide α-helix formation.
- Ellipsometry and liposome leakage assays to quantify membrane binding and integrity.
Main Results:
- Free LL-37 binds to lipid membranes in a concentration-dependent manner, causing defects and insertion into both leaflets at higher concentrations.
- LL-37 loaded into MAA microgels exhibits similar membrane localization and defect formation, primarily driven by released peptide.
- Microgel particles show minimal interaction with lipid membranes.
- Sustained release of LL-37 from MAA microgels significantly reduces the kinetics of its α-helix formation and membrane interaction.
Conclusions:
- Membrane interactions of LL-37 delivered via MAA microgels are predominantly mediated by the released peptide.
- The slow release kinetics from microgels modulate the peptide-membrane interaction dynamics, affecting peptide localization and bilayer structure.
- MAA microgels serve as effective carriers for LL-37, influencing its membrane interaction profile through controlled release.
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