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Probing Zinc-Protein-Chelant Interactions using Gold Nanoparticles Functionalized with Zinc-Responsive Polypeptides
Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska högskolan.ORCID-id: 0000-0003-3274-6029
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.ORCID-id: 0000-0002-1781-1489
Linköpings universitet, Institutionen för fysik, kemi och biologi, Tunnfilmsfysik. Linköpings universitet, Tekniska högskolan.
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.ORCID-id: 0000-0002-7001-9415
2014 (engelsk)Inngår i: Particle & particle systems characterization, ISSN 0934-0866, E-ISSN 1521-4117, Vol. 31, nr 11, s. 1127-1133Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The coordination of zinc by proteins and various other organic molecules is essential for numerous biological processes, such as in enzymatic catalysis, metabolism and signal transduction. Presence of small molecular chelants can have a profound effect on the bioavailability of zinc and affect critical Zn2+-protein interactions. Zn2+ chelators are also emerging therapeutics for Alzheimer’s diseases because of their preventive effect on zinc promoted amyloid formation. Despite the importance of zinc-protein-chelant interactions in biology and medicine, probing such interactions is  challenging. Here, we introduce an innovative approach for real-time characterization of zinc-protein-chelant interactions using gold nanoparticles (AuNPs) functionalized with a zinc-responsive protein mimetic polypeptide. The peptide functionalized AuNPs aggregate extensively in the presence of Zn2+, triggered by specific Zn2+-mediated polypeptide dimerization and folding, causing a massive red shift of the plasmon band. Chelants affects the Zn2+- polypeptide interaction and thus the aggregation differently depending on their concentrations, zincbinding affinities and coordination numbers, which affect the position of the plasmon band. This system is a simple and powerful tool that provides extensive information about the interactions of chelants in the formation of Zn2+ coordination complexes and is an interesting platform for development of bioanalytical techniques and characterization of chelation-based therapeutics.

sted, utgiver, år, opplag, sider
Wiley-VCH Verlagsgesellschaft, 2014. Vol. 31, nr 11, s. 1127-1133
Emneord [en]
Gold nanoparticles, zinc, peptide, chelation
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-106717DOI: 10.1002/ppsc.201400082ISI: 000344681700003OAI: oai:DiVA.org:liu-106717DiVA, id: diva2:718086
Tilgjengelig fra: 2014-05-19 Laget: 2014-05-19 Sist oppdatert: 2019-01-22bibliografisk kontrollert
Inngår i avhandling
1. Polypeptide functionalized gold nanoparticles for bioanalytical applications
Åpne denne publikasjonen i ny fane eller vindu >>Polypeptide functionalized gold nanoparticles for bioanalytical applications
2014 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Detection strategies that allow for simple, rapid, cost efficient and sensitive monitoring of proteins and their interactions with biomolecules are of great importance in drug development and diagnostics. This thesis describes the development of bioanalytical applications based on the tunable self-assembly of gold nanoparticles functionalized with a de novo designed polypeptide. Strategies for protein affinity sensing and for detection of several fundamentally important biological processes have been investigated, including Zn2+-mediated coordination between polypeptides and low molecular weight chelants and protease and phosphatase activity.

A Zn2+ responsive synthetic polypeptide designed to fold into a helix-loop-helix motif and dimerize into a four-helix bundle has been used to control the stability and self-assembly of gold nanoparticles. This polypeptide has a high negative net charge at neutral pH as a consequence of its many glutamic acid residues, efficiently preventing folding and dimerization due to charge repulsion. Zn2+ coordination provides a means to trigger folding and dimerization at neutral pH. The polypeptide can be readily attached to gold nanoparticles via a cysteine residue in the loop region, retaining its folding properties and responsiveness to Zn2+. The polypeptide functionalized gold nanoparticles display excellent colloidal stability but aggregate reversibly after addition of millimolar concentrations of Zn2+. Aggregates are dense with a defined interparticle distance corresponding to the size of the four-helix bundle, resulting in a distinct red shift of the localized surface plasmon resonance band.

Three completely different strategies for colorimetric biosensing have been developed, all being based on the same responsive hybrid nanomaterial. In the first strategy a synthetic receptor was co-immobilized on the gold nanoparticles together with the Zn2+ responsive polypeptide. Protein analyte binding to the receptor could be detected as this interaction sterically prevented aggregation induced by Zn2+. In the second strategy the reduction in colloidal stability caused by specific proteolytic cleavage of the immobilized polypeptide was exploited to monitor the enzymatic activity. The third strategy utilized the sensitivity of the system to small variations in Zn2+ concentration. The presence of low molecular weight chelants was found to influence the mode of aggregation, both by sequestering Zn2+ and through the formation of ternary complexes involving the polypeptides, which prevented dimerization and thus aggregation. This approach was further developed into a generic concept for phosphatase detection exploiting the different affinity of enzyme substrates and reaction products for Zn2+.

The flexibility of the different detection schemes enables detection of a large number of analytes by exploiting the tunable stability of the nanoparticles and the possibilities to effectively decouple the recognition event and the nanoparticle stability modulation.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 2014. s. 62
Serie
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1598
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-106719 (URN)10.3384/diss.diva-106719 (DOI)978-91-7519-321-2 (ISBN)
Disputas
2014-06-12, Plank, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 09:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2014-05-19 Laget: 2014-05-19 Sist oppdatert: 2019-11-19bibliografisk kontrollert

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