Nature Methods
- 4, 1023 - 1030 (2007)
Published online: 18 November 2007; | doi:10.1038/nmeth1131
Prion strain discrimination using luminescent conjugated polymersChristina J Sigurdson1, 6, K Peter R Nilsson1, 6, Simone Hornemann2, Giuseppe Manco1, Magdalini Polymenidou1, Petra Schwarz1, Mario Leclerc3, Per Hammarström4, Kurt Wüthrich2, 5 & Adriano Aguzzi11
UniversitätsSpital Zürich, Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, CH–8091 Zürich, Switzerland. 2
Institut für Molekularbiologie und Biophysik, ETH Zürich, CH-8093 Zürich, Switzerland. 3
Department of Chemistry, Vachon Building, Rue de la Médecine, Université Laval, Quebec City, G1K 7P4, Canada. 4
Department of Chemistry, Linköping University, 581 83 Linköping, Sweden. 5
Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA. 6
These authors contributed equally to this work.
Correspondence should be addressed to Adriano Aguzzi adriano.aguzzi@usz.ch The occurrence of multiple strains of prions may reflect conformational variability of PrPSc, a disease-associated, aggregated variant of the cellular prion protein, PrPC. Here we used luminescent conjugated polymers (LCPs), which emit conformation-dependent fluorescence spectra, for characterizing prion strains. LCP reactivity and emission spectra of brain sections discriminated among four immunohistochemically indistinguishable, serially mouse-passaged prion strains derived from sheep scrapie, chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), and mouse-adapted Rocky Mountain Laboratory scrapie prions. Furthermore, using LCPs we differentiated between field isolates of BSE and bovine amyloidotic spongiform encephalopathy, and identified noncongophilic deposits in prion-infected deer and sheep. We found that fibrils with distinct morphologies generated from chemically identical recombinant PrP yielded unique LCP spectra, suggesting that spectral characteristic differences resulted from distinct supramolecular PrP structures. LCPs may help to detect structural differences among discrete protein aggregates and to link protein conformational features with disease phenotypes.
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