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@ARTICLE{Rocco:153366,
author = {Rocco, Mattia and Molteni, Matteo and Ponassi, Marco and
Giachi, Guido and Frediani, Marco and Koutsioumpas,
Alexandros and Profumo, Aldo and Trevarin, Didier and
Cardinali, Barbara and Vachette, Patrice and Ferri, Fabio
and Pérez, Javier},
title = {{A} {C}omprehensive {M}echanism of {F}ibrin {N}etwork
{F}ormation {I}nvolving {E}arly {B}ranching and {D}elayed
{S}ingle- to {D}ouble-{S}trand {T}ransition from {C}oupled
{T}ime-{R}esolved {X}-ray/{L}ight-{S}cattering {D}etection},
journal = {Journal of the American Chemical Society},
volume = {136},
number = {14},
issn = {1520-5126},
address = {Washington, DC},
publisher = {American Chemical Society},
reportid = {FZJ-2014-02997},
pages = {5376 - 5384},
year = {2014},
abstract = {The formation of a fibrin network following fibrinogen
enzymatic activation is the central event in blood
coagulation and has important biomedical and
biotechnological implications. A non-covalent polymerization
reaction between macromolecular monomers, it consists
basically of two complementary processes:
elongation/branching generates an interconnected 3D scaffold
of relatively thin fibrils, and cooperative lateral
aggregation thickens them more than 10-fold. We have studied
the early stages up to the gel point by fast
fibrinogen:enzyme mixing experiments using simultaneous
small-angle X-ray scattering and wide-angle, multi-angle
light scattering detection. The coupled evolutions of the
average molecular weight, size, and cross section of the
solutes during the fibrils growth phase were thus recovered.
They reveal that extended structures, thinner than those
predicted by the classic half-staggered, double-stranded
mechanism, must quickly form. Following extensive modeling,
an initial phase is proposed in which single-bonded
“Y-ladder” polymers rapidly elongate before undergoing a
delayed transition to the double-stranded fibrils.
Consistent with the data, this alternative mechanism can
intrinsically generate frequent, random branching points in
each growing fibril. The model predicts that, as a
consequence, some branches in these expanding “lumps”
eventually interconnect, forming the pervasive 3D network.
While still growing, other branches will then undergo a
Ca2+/length-dependent cooperative collapse on the resulting
network scaffolding filaments, explaining their sudden
thickening, low final density, and basic mechanical
properties},
cin = {Neutronenstreuung ; JCNS-1 / JCNS (München) ; Jülich
Centre for Neutron Science JCNS (München) ; JCNS-FRM-II /
ICS-1},
ddc = {540},
cid = {I:(DE-Juel1)JCNS-1-20110106 /
I:(DE-Juel1)JCNS-FRM-II-20110218 /
I:(DE-Juel1)ICS-1-20110106},
pnm = {451 - Soft Matter Composites (POF2-451) / 54G - JCNS
(POF2-54G24)},
pid = {G:(DE-HGF)POF2-451 / G:(DE-HGF)POF2-54G24},
experiment = {EXP:(DE-MLZ)External-20140101},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000334572200039},
doi = {10.1021/ja5002955},
url = {https://juser.fz-juelich.de/record/153366},
}