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Peptide-Microgel Interactions in the Strong Coupling Regime
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.ORCID iD: 0000-0002-0895-1180
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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2012 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, no 35, 10964-10975 p.Article in journal (Refereed) Published
Abstract [en]

The interaction between lightly cross-linked poly(acrylic acid) microgels and oppositely charged peptides was investigated as a function of peptide length, charge density, pH, and salt concentration, with emphasis on the strong coupling regime at high charge contrast. By micromanipulator-assisted light microscopy, the equilibrium volume response of single microgel particles upon oligolysine and oligo(lysine/alanine) absorption could be monitored in a controlled fashion. Results show that microgel deswelling, caused by peptide binding and network neutralization, increases with peptide length (3 < 5 < 10) and charge density (30% < 50% < 100%). Furthermore, oligomer-induced microgel deswelling was more pronounced at pH 5 than at pH 8, reflecting the lower network charge density in the former case (pK(a) for the isolated acrylic acid approximate to 4.7). In order to describe these highly coupled systems, a model was developed, in which counterion/peptide-mediated electrostatic attraction between the network chains is described using an exponential force law, and the network elasticity by the inverse Langevin theory. The model was used to calculate the composition of microgels in contact with reservoir solutions of peptides and simple electrolytes. At high electrostatic coupling, the calculated swelling curves were found to display first-order phase transition behavior. The model was demonstrated to capture pH- and electrolyte-dependent microgel swelling, as well as effects of peptide length and charge density on microgel deswelling. The analysis demonstrated that the peptide charge (length), rather than the peptide charge density, determines microgel deswelling. Furthermore, a transition between continuous and discrete network collapse was identified, consistent with experimental results in the present investigations, as well as with results from the literature on microgel deswelling caused by multivalent cations.

Place, publisher, year, edition, pages
2012. Vol. 116, no 35, 10964-10975 p.
National Category
Chemical Sciences
URN: urn:nbn:se:uu:diva-182754DOI: 10.1021/jp306121hISI: 000308339400060OAI: oai:DiVA.org:uu-182754DiVA: diva2:561413
Available from: 2012-10-18 Created: 2012-10-15 Last updated: 2016-04-27Bibliographically approved
In thesis
1. Microgel Interactions with Peptides and Proteins: Consequence of Peptide and Microgel Properties
Open this publication in new window or tab >>Microgel Interactions with Peptides and Proteins: Consequence of Peptide and Microgel Properties
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Microgels are lightly cross-linked hydrogel particles in the sub-micrometer to micrometer size range with a capacity to drastically change their volume in response to changes in the external environment. Microgels have an ability to bind and store substances such as biomacromolecular drugs, notably proteins and peptides, and release them upon stimuli, making them potential candidates as drug delivery vehicles and functional biomaterials. This thesis aims at clarifying important factors affecting peptide-microgel interactions. These interactions were studied by micromanipulator-assisted light and fluorescence microscopy focusing on microgel deswelling in response to peptide binding, as well as re-swelling in response to peptide release or enzymatic degradation. To evaluate peptide uptake in microgels, solution depletion measurements were used whereas the peptide secondary structure was investigated by circular dichroism. In addition, the peptide and enzyme distribution within microgels was analyzed with confocal microscopy.

Results presented in this thesis demonstrate that peptide incorporation into microgels, as well as peptide-induced microgel deswelling, increases with peptide length and charge density. In addition, results demonstrate that the peptide charge (length) rather than peptide charge density determines microgels deswelling. End-to-end cyclization is shown to not noticeably influence peptide-microgel interactions, suggesting that peptide cyclization can be used in combination with oppositely charged microgel carriers to improve the proteolytic and chemical stability of the peptide compared to the corresponding linear variant. Peptide secondary structure is found to drastically affect peptide incorporation into, and release from, oppositely charged microgels. Furthermore, it is shown that microgel charge density, peptide molecular weight, and enzyme concentration all greatly influence microgel bound peptide degradation. Of importance for applications, protective effects of microgels against proteolytic peptide degradation are observed only at sufficiently high microgel charge densities. Enzyme-mediated microgel degradation is shown to increase with increasing enzyme concentration, while an increased peptide loading in microgels causes a concentration-dependent decrease in microgel degradation.

Taken together, results obtained in this work have provided some insight into factors of importance for rational use of microgels as delivery systems for protein or peptide drugs, but also in a host of other biomedical applications using weakly cross-linked polymer systems.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 65 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 196
Binding, Degradation, Enzyme, Gel, Hydrogel, Microgel, Peptide, Protein, Release
National Category
Pharmaceutical Sciences Physical Chemistry Materials Engineering
Research subject
Pharmaceutical Physical Chemistry
urn:nbn:se:uu:diva-242893 (URN)978-91-554-9157-4 (ISBN)
Public defence
2015-03-20, B21, BMC, Husargatan 3, Uppsala, 09:15 (English)
Available from: 2015-02-24 Created: 2015-02-02 Last updated: 2015-03-11

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Hansson, PerMånsson, RonjaMalmsten, Martin
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