| 1. |
- Herland, Anna, et al.
(författare)
-
Alignment of a conjugated polymer onto amyloid-like protein fibrils
- 2007
-
Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 3:2, s. 318-325
-
Tidskriftsartikel (refereegranskat)abstract
- The amyloid-like fibril is a biomolecular nanowire template of very high stability. Here we describe the coordination of a conjugated polyelectrolyte, poly(thiophene acetic acid) (PTAA), to bovine insulin fibrils with widths of <10 nm and lengths of up to more than 10 m. Fibrils complexed with PTAA are aligned on surfaces through molecular combing and transfer printing. Single-molecule spectroscopy techniques are applied to chart spectral variation in the emission of these wires. When these results are combined with analysis of the polarization of the emitted light, we can conclude that the polymer chains are preferentially aligned along the fibrillar axis.
|
|
| 2. |
- Herland, Anna, 1979-, et al.
(författare)
-
Conjugated polymers as optical probes for protein interactions and protein conformations
- 2007
-
Ingår i: Macromolecular rapid communications. - : Wiley. - 1022-1336 .- 1521-3927. ; 28:17, s. 1703-1713
-
Tidskriftsartikel (refereegranskat)abstract
- There is a need for highly sensitive, multi-parallel protein sensors within diagnostics and proteomic research. Conjugated polymers (CPs) have been demonstrated as highly sensitive optical probes for protein biosensing. Compared to small molecules, the polymeric probe has the possibility of multiple interactions and a collective response, which enhances the sensor signal. The optical output is colorimetric or, more sensitive, fluorescence based, including Förster energy transfer and changes in the emission wavelengths and/or intensity. Using CPs, many interesting protein detection events have been demonstrated, e.g., protein interactions, enzymatic activity, amyloid fibril formation, and detection by aptamers. CPs have also been successfully used to stain bacterial, cellular, and tissue samples. © 2007 WILEY-VCH Verlag GmbH & Co. KGaA.
|
|
| 3. |
|
|
| 4. |
- Nilsson, K. Peter R., et al.
(författare)
-
Imaging distinct conformational states of amyloid-beta fibrils in Alzheimer's disease using novel luminescent probes
- 2007
-
Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 2:8, s. 553-560
-
Tidskriftsartikel (refereegranskat)abstract
- Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1–42 peptide (Aβ1–42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1–42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APP swe) of Alzheimer’s disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.
|
|
| 5. |
- Nilsson, Peter, et al.
(författare)
-
Imaging distinct conformational states of amyloid-β fibrils in Alzheimer's disease using novel luminescent probes
- 2007
-
Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 2:8, s. 553-560
-
Tidskriftsartikel (refereegranskat)abstract
- Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimer's disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.
|
|
| 6. |
- Åslund, Andreas, et al.
(författare)
-
Studies of luminescent conjugated polythiophene derivatives-Enhanced spectral discrimination of protein conformational states
- 2007
-
Ingår i: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 18:6, s. 1860-1868
-
Tidskriftsartikel (refereegranskat)abstract
- Improved probes for amyloid fibril formation are advantageous for the early detection and better understanding of this disease-associated process. Here, we report a comparative study of eight luminescent conjugated polythiophene derivates (LCPs) and their discrimination of a protein (insulin) in the native or amyloid-like fibrillar state. For two of the LCPs, the synthesis is reported. Compared to their monomer-based analogues, trimer-based LCPs showed significantly better optical signal specificity for amyloid-like fibrils, seen from increased quantum yield and spectral shift. The trimer-based LCPs alone were highly quenched and showed little interaction with native insulin, as seen from analytical ultracentrifugation and insignificant spectral differences from the trimer-based LCP in buffered and native protein solution. Hence, the trimer-based LCPs showed enhanced discrimination between the amyloid-like fibrillar state and the corresponding native protein.
|
|
