Abstract
Supramolecular assembly and PEGylation (attachment of a polyethylene glycol polymer chain) of peptides can be an effective strategy to develop antimicrobial peptides with increased stability, antimicrobial efficacy and hemocompatibility. However, how the self-assembly properties and PEGylation affect their lipid membrane interaction is still an unanswered question. In this work, we use state-of-the-art small angle X-ray and neutron scattering (SAXS/SANS) together with neutron reflectometry (NR) to study the membrane interaction of a series of multidomain peptides, with and without PEGylation, known to self-assemble into nanofibers. Our approach allows us to study both how the structure of the peptide and the membrane are affected by the peptide-lipid interactions. When comparing self-assembled peptides with monomeric peptides that are not able to undergo assembly due to shorter chain length, we found that the nanofibers interact more strongly with the membrane. They were found to insert into the core of the membrane as well as to absorb as intact fibres on the surface. Based on the presented results, PEGylation of the multidomain peptides leads to a slight net decrease in the membrane interaction, while the distribution of the peptide at the interface is similar to the non-PEGylated peptides. Based on the structural information, we showed that nanofibers were partially disrupted upon interaction with phospholipid membranes. This is in contrast with the considerable physical stability of the peptide in solution, which is desirable for an extendedin vivocirculation time.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | RSC Advances |
| Vol/bind | 10 |
| Udgave nummer | 58 |
| Sider (fra-til) | 35329-35340 |
| Antal sider | 12 |
| ISSN | 2046-2069 |
| DOI | |
| Status | Udgivet - 24 sep. 2020 |
| Udgivet eksternt | Ja |
Bibliografisk note
Funding Information:JEN, MC and RL gratefully acknowledge NordForsk (Project no. 82004) for financial support. MC thanks the Swedish Research Council for financial support (2018-03990 and 2018-0483). This work was supported by the U.S. National Science Foundation (Award: DMR-1824614 to H. D and S. Y). The authors would like to thank ISIS neutron facility for providing neutron reflectometry beamtime at the INTER beamline (DOI:10.5286/ISIS.E.101138375) and SANS beamtime at SANS2D beamline (DOI:10.5286/ISIS.E.RB1920565and DOI:10.5286/ISIS.E.RB1920656). The authors are also grateful to the ILL for providing beamtime (DOI:10.5291/ILL-DATA.9-13-743) and for the help of Sarah Waldie at ILL during the NR experiments at Figaro, and the PCSM lab for support during the ILL experiments. We acknowledge use of the Norwegian national infrastructure for X-ray diffraction and scattering (RECX). Further, we are in depth to Dr Lutz Willner at Forschungszentrum Jülich GmbH, for synthesising the deuterated PEG in compound D-P-3W62.
Funding Information:
JEN, MC and RL gratefully acknowledge NordForsk (Project no. 82004) for nancial support. MC thanks the Swedish Research Council for nancial support (2018-03990 and 2018-0483). This work was supported by the U.S. National Science Foundation (Award: DMR-1824614 to H. D and S. Y). The authors would like to thank ISIS neutron facility for providing neutron reectom-etry beamtime at the INTER beamline (DOI: 10.5286/ ISIS.E.101138375) and SANS beamtime at SANS2D beamline (DOI: 10.5286/ISIS.E.RB1920565 and DOI: 10.5286/ ISIS.E.RB1920656). The authors are also grateful to the ILL for providing beamtime (DOI: 10.5291/ILL-DATA.9-13-743) and for the help of Sarah Waldie at ILL during the NR experiments at Figaro, and the PCSM lab for support during the ILL experiments. We acknowledge use of the Norwegian national infrastructure for X-ray diffraction and scattering (RECX). Further, we are in depth to Dr Lutz Willner at Forschungszentrum Jülich GmbH, for synthesising the deuterated PEG in compound D–P– 3W62.
Publisher Copyright:
© The Royal Society of Chemistry 2020.