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@ARTICLE{Wang:614231,
author = {Wang, Mengying and Thünauer, Roland and Schubert, Robin
and Gevorgyan, Susanna and Lorenzen, Kristina and Brognaro,
Hévila and Betzel, Christian},
title = {{F}ormation kinetics and physicochemical properties of
mesoscopic {A}lpha-{S}ynuclein assemblies modulated by
sodium chloride and a distinct pulsed electric field},
journal = {Soft matter},
volume = {19},
number = {7},
issn = {1744-683X},
address = {London},
publisher = {Royal Soc. of Chemistry},
reportid = {PUBDB-2024-05771},
pages = {1363 - 1372},
year = {2023},
abstract = {Alpha-Synuclein (ASN), a presynaptic protein, has been
widely reported to form amyloid-rich hydrogel clusters
through liquid–liquid phase separation (LLPS) and
liquid-to-solid transition. However, in-depth investigations
about the parameters that influence the assembling kinetics,
structures, and physicochemical properties of intermediate
ASN assemblies are still missing. Therefore, we monitored
for the first time the assembling and ordering kinetics of
ASN by polarized/depolarized light scattering (DLS/DDLS)
under the effect of ionic strength and a pulsed electric
field (EF), followed by characterizing the resultant ASN
assemblies applying thermostability assays,
fluorescence/autofluorescence assays, and TEM. The
underlying molecular mechanism was discussed based on
experimental evidence. Results showed that in the presence
of 150–250 mM NaCl, monomeric ASN is highly soluble in a
temperature range of 20–70 °C and could form dissoluble
liquid dense clusters via LLPS in crowded environments,
while the ionic strength of 50 mM NaCl could trigger
conformational changes and attractive diffusion interactions
of ASN monomers towards the formation of mesoscopic
assemblies with ordered internal structures and high
thermostabilities. We discovered that pulsed EFs and ionic
strength can modulate effectively the thermostability and
autofluorescence effect of mesoscopic ASN assemblies by
tuning the molecular interaction and arrangement.
Remarkably, a specie of thermostable ASN assemblies showing
a maximum autofluorescence emission at approx. 700 nm was
synthesized applying 250 mM NaCl and the distinct pulsed EF,
which could be attributed to the increase of β-sheet
structures and hydrogen-bond networks within ASN assemblies.
In summary, the presented data provide novel insights for
modulating the growth kinetics, structures, and
physicochemical properties of bio-macromolecular mesoscopic
assemblies.},
cin = {CSSB-CF-ALFM},
ddc = {530},
cid = {I:(DE-H253)CSSB-CF-ALFM-20210629},
pnm = {899 - ohne Topic (POF4-899) / DFG project
G:(GEPRIS)390715994 - EXC 2056: CUI: Advanced Imaging of
Matter (390715994) / DFG project G:(GEPRIS)194651731 - EXC
1074: Hamburger Zentrum für ultraschnelle Beobachtung
(CUI): Struktur, Dynamik und Kontrolle von Materie auf
atomarer Skala (194651731)},
pid = {G:(DE-HGF)POF4-899 / G:(GEPRIS)390715994 /
G:(GEPRIS)194651731},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36723049},
UT = {WOS:000920904800001},
doi = {10.1039/D2SM01615J},
url = {https://bib-pubdb1.desy.de/record/614231},
}