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Effect of hydrophobicity on the interaction between antimicrobial peptides and poly(acrylic acid) microgels
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Section of Dermatology and Venerology, Department of Clinical Sciences, Lund University.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2010 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 114, no 3, 1307-1313 p.Article in journal (Refereed) Published
Abstract [en]

The influence of peptide hydrophobicity on the interaction between antimicrobial peptides and poly(acrylic, acid) microgels wits studied by end-tagging the kininogen-derived antimicrobial peptide GKHKNKGKKNGKHNGWK (GKH17) and its truncated variant KNKGKKNGKH (KNK10) with oligotryptophan groups of different lengths. Microgel deswelling and reswelling in response to peptide binding and release was studied by micromanipulator-assisted light- and fluorescence microscopy, peptide uptake in microgels was determined from solution depletion measurements, and peptide oligomerization was monitored by fluorescence spectroscopy. Results showed that oligomerizition/aggregation of the hydrophobically end-tagged peptides is either absent or characterized by exposure of the tryptophan residues to the aqueous ambient, the latter suggesting small aggregation numbers. In addition, peptide uptake and affinity to the poly(acrylic acid) microgels increase with the number of trypthophan residues in the hydrophobic end tag, whereas peptide-induced microgel deswelling kinetics did not display this tag-length dependence to the same extent. Instead, long end tags resulted in anomalous shell formation, opposing further peptide-induced network deswelling. Theoretical modeling suggested that the deswelling kinetics in response to peptide binding is largely controlled by stagnant layer diffusion, but also that for peptides with Sufficiently long hydrophobic tags, the shell constitutes an additional diffusion barrier, thus resulting in slower microgel deswelling. In addition, GKH17 and KNK10 peptides lacking the tryptophan end tags were Substantially released on reducing peptide-microgel electrostatic interactions through addition of salt, an effect more pronounced for the shorter KNK10 peptide, whereas the hydrophobically end-tagged peptides remained bound to the microgels also at high ionic strength.

Place, publisher, year, edition, pages
2010. Vol. 114, no 3, 1307-1313 p.
National Category
Pharmaceutical Sciences Chemical Sciences Medical and Health Sciences
URN: urn:nbn:se:uu:diva-109209DOI: 10.1021/jp910068tISI: 000273672300012OAI: oai:DiVA.org:uu-109209DiVA: diva2:271537
Available from: 2009-10-12 Created: 2009-10-12 Last updated: 2011-01-04Bibliographically approved
In thesis
1. Interaction Between Microgels and Oppositely Charged Peptides
Open this publication in new window or tab >>Interaction Between Microgels and Oppositely Charged Peptides
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lightly cross-linked polyelectrolyte microgels are materials with interesting properties for a range of applications. For instance, the volume of these particles can be drastically changed in response to pH, ionic strength, temperature, or the concentration of specific ions and metabolites. In addition, microgel particles can bind substantial amounts of oppositely charged substances, such as proteins and peptides, and release them upon changes in the external environment. Consequently, microgels have potential in catalysis, photonics, biomaterials, and not at least, as protective and stimuli-sensitive carriers for protein and peptide drugs.

In this thesis, the interaction between anionic microgels and cationic peptides was investigated by monitoring microgel deswelling and reswelling in response to peptide binding and release using micromanipulator-assisted light microscopy. In addition, peptide distribution in microgels was analyzed with confocal laser scanning microscopy and peptide uptake determined with solution depletion measurements. The aim of the thesis was to clarify how parameters such as peptide size, charge density, pH, ionic strength and hydrophobicity influences the peptide binding to, distribution in and release from, polyelectrolyte microgels.

Results obtained in this thesis show that electrostatic attraction is a prerequisite for interaction to occur although non-electrostatic contributions are responsible the finer details of the interactions. The size and charge density of the interacting peptides play a major role, as large and highly charged peptides are restricted to enter and interact with the microgel core, thus displaying a surface-confined distribution. The peptide-microgel interaction strength is highly reflected in the probability of peptides to be detached from the gel network. For instance, reducing the electrostatic interactions by adding salt induces significant peptide release of sufficiently small and moderately charged peptides, whereas longer and more highly charged peptides is retained in the microgel network due to the strong interaction, insufficient salt screening, and gel network pore size restriction. Decreasing the charge density of microgel network and/or peptides increases the probability for peptide detachment tremendously.

To summarize, interactions occurring in oppositely charged microgel-peptide systems can be tuned by varying parameters such as charge density and peptide size and through this, the peptide uptake, distribution and release can be controlled to alter the performance of microgels in peptide drug delivery.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 68 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 113
antimicrobial peptides, binding, cationic peptides, confocal microscopy, deswelling, distribution, electrostatic, homopolypeptides, microgels, peptides, release, swelling
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Physical Chemistry
urn:nbn:se:uu:diva-109203 (URN)978-91-554-7635-9 (ISBN)
Public defence
2009-11-27, B21, BMC, Husargatan 3, Uppsala, 09:15 (English)
Available from: 2009-11-06 Created: 2009-10-12 Last updated: 2009-11-06

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