Optical Reporting by Conjugated Polymers via Conformational Changes - Advanced Fluorescence Reporters in Chemistry and Biology - page 410

Fig. 19 (a) Chemical structure of the zwitter-ionic polythiophene derivative, tPTT. (b) Confor-
mational heterogeneity of amyloid plaques in tPTT-stained mouse brain with A b deposits.
Fluorescence microscope image showing localized distribution of amyloid plaques in the cerebral
cortex. The compact plaques with diffuse exteriors show an orange periphery and a green center as
indicated with arrows . In addition, a compact core plaque showing intense orange fluorescence is
also visible. (c) Bar plot of the ratio of the fluorescence intensity of the green component
(integrated between 543 and 564 nm) and the red component (integrated between 639 and
661 nm) of the spectra from the individual plaques 1-4. For all plaques, the periphery shows a
larger red contribution than the center [ 34 ]

spectra over the region of distinct amyloid deposits (Fig. 19 ). The spectra revealed a
range of colors from green to red appearing as though the packing conformation or
the structural arrangement of the plaques varied from the plaque center to the
periphery. To show that the polymer was actually able to distinguish between packing
or conformational variation within the same peptide sequence, they showed that the
polymer was able to show similar spectral distinctions between A 1-42 fibrils formed

under different conditions in vitro. Hence, the unique optical properties of CPs could
be used to map the conformational heterogeneity in A

b

deposits both in tissue and
solution. These findings could lead to novel ways of diagnosing Alzheimer's disease
(AD) and also provide a new method for studying the pathology of the disease in a
more refined manner. The technique has the potential to be valuable for establishing a
correlation between the type of deposits and the severity of AD. However, further
studies are necessary to understand the correlation of the spectroscopic read out from
the LCP and the molecular structure of the protein aggregate. Nevertheless, the LCPs
can be useful for comparison of heterogenic protein aggregates in well-defined
experimental systems.
Heterogenic protein aggregates can also be found in other protein aggregation
disorders, such as the infectious prion diseases. These diseases are caused by a
proteinaceous agent called PrP Sc , a misfolded and aggregated version of the normal
prion protein. In addition, prions can occur as different strains, and the prion strain
phenomenon is most likely encoded in the tertiary or quaternary structure of the
prion aggregates. This belief was also verified when CP staining was applied to
protein aggregates in brain sections from mice infected with distinct prion strains
[ 35 ]. The LCPs bound specifically to the prion deposits and different prion strains
could be differentiated due to a distinct spectral signature from the CP (Fig. 20 ). The
anionic LCP, PTAA, was shown to emit light of different wavelengths when bound
to distinct protein deposits associated with a specific prion strain, such as murine

b