uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Interaction of Peptidomimetics with Bilayer Membranes: Biophysical Characterization and Cellular Uptake
Show others and affiliations
2012 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 28, no 11, 5167-5175 p.Article in journal (Refereed) Published
Abstract [en]

Enzymatically stable cell-penetrating alpha-peptide/beta-peptoid peptidomimetics constitute promising drug delivery vehicles for the transport of therapeutic biomacromolecules across membrane barriers. The aim of the present study was to elucidate the mechanism of peptidomimetic-lipid bilayer interactions. A series of peptidomimetics consisting of alternating cationic and hydrophobic residues displaying variation in length and N-terminal end group were applied to fluid-phase, anionic lipid bilayers, and their interaction was investigated using isothermal titration calorimetry (ITC) and ellipsometry. Titration of lipid vesicles into solutions of peptidomimetics resulted in exothermic adsorption processes, and the interaction of all studied peptidomimetics with anionic lipid membranes was found to be enthalpy-driven. The enthalpy and Gibbs free energy (Delta G) proved more favorable with increasing chain length. However, not all charges contribute equally to the interaction, as evidenced by the charge-normalized Delta G being inversely correlated to the sequence length. Ellipsometry data suggested that the hydrophobic residues also played an important role in the interaction process. Furthermore, Delta G extracted from ellipsometry data showed good agreement with that obtained with ITC. To further elucidate their interaction with biological membranes, quantitative uptake and cellular distribution were studied in proliferating HeLa cells by flow cytometry and confocal microscopy. The cellular uptake of carboxyfluorescein-labeled peptidomimetics showed a similar ranking as that obtained from the adsorbed amount, and binding energy to model membranes demonstrated that the initial interaction with the membrane is of key importance for the cellular uptake.

Place, publisher, year, edition, pages
2012. Vol. 28, no 11, 5167-5175 p.
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-172820DOI: 10.1021/la204033uISI: 000301636900032OAI: oai:DiVA.org:uu-172820DiVA: diva2:516214
Available from: 2012-04-17 Created: 2012-04-16 Last updated: 2012-04-17Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Malmsten, Martin
By organisation
Department of Pharmacy
In the same journal
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 200 hits
ReferencesLink to record
Permanent link

Direct link