Carrier peptide interactions with liposome membranes induce reversible clustering by surface adsorption and shape deformation
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The cell-penetrating peptide penetratin and its analogues shuffle and penetramax have been used as carrier peptides for oral delivery of therapeutic peptides such as insulin. Their mechanism of action for this purpose is not fully understood but is believed to depend on the interactions of the peptide with the cell membrane. In the present study, peptide-liposome interactions were investigated using advanced biophysical techniques including small-angle neutron scattering and fluorescence lifetime imaging microscopy. Liposomes were used as a model system for the cell membrane. All the investigated carrier peptides induced liposome clustering at a specific peptide/lipid ratio. However, distinctively different types of membrane interactions were observed, as the liposome clustering was irreversible for penetratin, but fully or partly reversible for shuffle and penetramax, respectively. All three peptides were found to adsorb to the surface of the lipid bilayers, while only shuffle and penetramax led to shape deformation of the liposomes. Importantly, the peptide interactions did not disrupt the liposomes under any of the investigated conditions, which is advantageous for their application in drug delivery. This detailed insight on peptide-membrane interactions is important for understanding the mechanism of peptide-based excipients and the influence of peptide sequence modifications.
| Original language | English |
|---|---|
| Journal | Journal of Colloid and Interface Science |
| Volume | 650 |
| Issue number | Part B |
| Pages (from-to) | 1821-1832 |
| ISSN | 0021-9797 |
| DOIs | |
| Publication status | Published - 2023 |
Bibliographical note
Funding Information:
This project was funded by the Novo Nordisk Foundation (Grand Challenge Programme: NNF16OC0021948 for the Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), University of Copenhagen). V.F. acknowledges VILLUM FONDEN for funding the project via the Villum Young Investigator grant “Protein Superstructures as Smart Biomaterials (ProSmart)” 2018-2023 (19175). This work benefited from the use of the SasView application, originally developed under NSF Award DMR-0520547. SasView also contains code developed with funding from the EU Horizon 2020 programme under the SINE2020 project Grant No 654000. We acknowledge the CFIM (University of Copenhagen) for cryo-TEM. Illustrations were created with icons from BioRender [42].
Funding Information:
This project was funded by the Novo Nordisk Foundation (Grand Challenge Programme: NNF16OC0021948 for the Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), University of Copenhagen). V.F. acknowledges VILLUM FONDEN for funding the project via the Villum Young Investigator grant “Protein Superstructures as Smart Biomaterials (ProSmart)” 2018-2023 (19175). This work benefited from the use of the SasView application, originally developed under NSF Award DMR-0520547. SasView also contains code developed with funding from the EU Horizon 2020 programme under the SINE2020 project Grant No 654000. We acknowledge the CFIM (University of Copenhagen) for cryo-TEM. Illustrations were created with icons from BioRender [42] .
Publisher Copyright:
© 2023 The Authors
- Cell-penetrating peptide, Fluorescence lifetime imaging microscopy, Mechanism, Membrane interaction, Small-angle neutron scattering
Research areas
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