Page 376 - Organic Electronics in Sensors and Biotechnology

Luminescent Conjugated Polymers for Staining and Characterization of Amyloid Deposits 353

variance of the protein deposits associated with the distinct prion
strains. By taking recombinant mouse prion protein (mPrP) and con-
verting it to two different types of amyloid fibrils by using varying
conditions for fibrillation, Sigurdson et al. were able to show that the
emission profile of PTAA could be used to distinguish the two fibril
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preparations (Fig. 9.10c). As these two preparations of fibrils were
chemically identical, having the same protein (mPrP) and being dia-
lyzed against the same buffer, the spectral differences seen for PTAA
were most likely due to structural differences between the fibrils.
Hence, LCPs provide structural insights regarding the morphology
of individual protein deposits and can be used as a complementary
technique to conventional staining protocols for the characterization
of protein deposits associated with individual prion strains. These
findings might be of great value, as phenomena similar to those
occurring in prion strains may be much more frequent than is now
appreciated, and may extend to additional protein misfolding and
aggregation disorders. As mentioned previously, strainlike confor-
mational variants have been described for A-beta aggregation, which
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underlies AD. LCPs might therefore aid in the fundamental under-
standing of conformational protein variants in a wide range of pro-
tein misfolding disorders. In addition, LCPs could improve the preci-
sion of diagnoses of protein aggregation diseases and facilitate
analysis of amyloid maturity and origin.

9.4.3 Toward in Vivo Staining of Amyloid Deposits
Clearly, there is much to be gained through a multidisciplinary scien-
tific approach; the integration of information can provide new insight
and discoveries within diverse fields of research. Unexpectedly, con-
jugated polymer materials that originate from electronics and solar
cells have provided novel insights into the biology and pathology of
protein aggregation diseases. Apparently, the spectral information
from LCPs will be useful to gain more information regarding the
molecular details of the protein aggregation process and the patho-
logical events underlying protein aggregation diseases. However,
there is still a great extent of basic research that can be performed to
take full advantage of the technique.
One tantalizing possibility is to develop LCPs that can be used for
in vivo imaging of protein aggregates. In this regard, smaller, appro-
priately functionalized, but still selective LCPs that are able to cross
the blood-brain barrier (BBB) need to be synthesized. These dyes can
be utilized in powerful multiphoton imaging applications for in vivo
imaging of protein aggregates, since previously reported LCPs have
been shown to have an excellent cross-sectional area compared to
small fluorescent dyes. 110, 113 However, these LCPs having a molecular
weight between 1000 and 5000 Da will not cross the BBB, so chemical
design of smaller, well-defined oligomeric thiophene molecules is