Abstract
The development of new sensitive methods for the detailed collection of conformational and morphological information about amyloids is crucial for the elucidation of critical questions regarding aggregation processes in neurodegenerative diseases. The combined approach of two-photon and time-resolved fluorescence spectroscopy described in this report interrogates the early conformational dynamics seen in soluble oligomers of amyloid-β(1-42). Concentration-dependent aggregation studies using two-photon absorption show enhanced sensitivity toward conformational changes taking place in the secondary structure of the amyloid peptide as aggregation proceeds. Fluorescence lifetimes and changes in anisotropy values indicate Förster-type energy transfer occurring as a function of aggregation state. The sensitivity of our two-photon methodology is compared to that of circular dichroism (CD) spectroscopy, and the results indicate that the two-photon absorption cross-section method exhibits superior sensitivity. A theoretical model is developed that, together with electronic structure calculations, explains the change in cross section as a function of aggregation in terms of interacting transition dipoles for aggregates showing stacked or parallel structures. This suggests that the two-photon method provides a sensitive alternative to CD spectroscopy while avoiding many of the inherent challenges particular to CD data collection. The implication of this finding is significant, as it indicates that a two-photon-based technique used in conjunction with time-resolved fluorescence might be able to reveal answers to conformational questions about amyloid-β(1-42) that are presently inaccessible with other techniques.
| Original language | English |
|---|---|
| Pages (from-to) | 2351-2359 |
| Number of pages | 9 |
| Journal | Journal of Physical Chemistry B |
| Volume | 118 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Mar 6 2014 |
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ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Materials Chemistry
- Surfaces, Coatings and Films
Cite this
Two-photon and time-resolved fluorescence spectroscopy as probes for structural determination in amyloid-β peptides and aggregates. / Clark, Travis B.; Ziółkowski, Marcin; Schatz, George C; Goodson, Theodore.
In: Journal of Physical Chemistry B, Vol. 118, No. 9, 06.03.2014, p. 2351-2359.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Two-photon and time-resolved fluorescence spectroscopy as probes for structural determination in amyloid-β peptides and aggregates
AU - Clark, Travis B.
AU - Ziółkowski, Marcin
AU - Schatz, George C
AU - Goodson, Theodore
PY - 2014/3/6
Y1 - 2014/3/6
N2 - The development of new sensitive methods for the detailed collection of conformational and morphological information about amyloids is crucial for the elucidation of critical questions regarding aggregation processes in neurodegenerative diseases. The combined approach of two-photon and time-resolved fluorescence spectroscopy described in this report interrogates the early conformational dynamics seen in soluble oligomers of amyloid-β(1-42). Concentration-dependent aggregation studies using two-photon absorption show enhanced sensitivity toward conformational changes taking place in the secondary structure of the amyloid peptide as aggregation proceeds. Fluorescence lifetimes and changes in anisotropy values indicate Förster-type energy transfer occurring as a function of aggregation state. The sensitivity of our two-photon methodology is compared to that of circular dichroism (CD) spectroscopy, and the results indicate that the two-photon absorption cross-section method exhibits superior sensitivity. A theoretical model is developed that, together with electronic structure calculations, explains the change in cross section as a function of aggregation in terms of interacting transition dipoles for aggregates showing stacked or parallel structures. This suggests that the two-photon method provides a sensitive alternative to CD spectroscopy while avoiding many of the inherent challenges particular to CD data collection. The implication of this finding is significant, as it indicates that a two-photon-based technique used in conjunction with time-resolved fluorescence might be able to reveal answers to conformational questions about amyloid-β(1-42) that are presently inaccessible with other techniques.
AB - The development of new sensitive methods for the detailed collection of conformational and morphological information about amyloids is crucial for the elucidation of critical questions regarding aggregation processes in neurodegenerative diseases. The combined approach of two-photon and time-resolved fluorescence spectroscopy described in this report interrogates the early conformational dynamics seen in soluble oligomers of amyloid-β(1-42). Concentration-dependent aggregation studies using two-photon absorption show enhanced sensitivity toward conformational changes taking place in the secondary structure of the amyloid peptide as aggregation proceeds. Fluorescence lifetimes and changes in anisotropy values indicate Förster-type energy transfer occurring as a function of aggregation state. The sensitivity of our two-photon methodology is compared to that of circular dichroism (CD) spectroscopy, and the results indicate that the two-photon absorption cross-section method exhibits superior sensitivity. A theoretical model is developed that, together with electronic structure calculations, explains the change in cross section as a function of aggregation in terms of interacting transition dipoles for aggregates showing stacked or parallel structures. This suggests that the two-photon method provides a sensitive alternative to CD spectroscopy while avoiding many of the inherent challenges particular to CD data collection. The implication of this finding is significant, as it indicates that a two-photon-based technique used in conjunction with time-resolved fluorescence might be able to reveal answers to conformational questions about amyloid-β(1-42) that are presently inaccessible with other techniques.
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UR - http://www.scopus.com/inward/citedby.url?scp=84897734496&partnerID=8YFLogxK
U2 - 10.1021/jp500883s
DO - 10.1021/jp500883s
M3 - Article
C2 - 24502657
AN - SCOPUS:84897734496
VL - 118
SP - 2351
EP - 2359
JO - Journal of Physical Chemistry B Materials
JF - Journal of Physical Chemistry B Materials
SN - 1520-6106
IS - 9
ER -