Biomedical Engineering Reference
In-Depth Information
Fibrin monomers
Fibrinogen
Thrombin
Fibrinopeptides
Protofibril
Fibrin polymer
6.2
Schematics showing the process of fi brin assembly using the
trinodular model. Fibrinogen is cleaved by thrombin to form fi brin
monomers after the release of fi brinopeptides. The two-stranded
protofi bril is formed by the non-covalent binding among
complementary binding sites located in D and E domains. Fibrin
polymer is formed by lateral association of protofi brils. The fi nal step
of the fi brin assembly is the crosslinking among adjacent D domains
proteolyzed by thrombin-activated factor XIIIa.
The fi nal step of the fi brin assembly is the reciprocal crosslinking process
as amide bonds are formed between adjacent γ and Aα chains and among γ
chains of adjacent D domains.
55-57
Fibrin assembly eventually results in an extensive network with intercon-
necting fi brin fi bers, which acts as a strong insoluble plug for hemostasis.
Within this crosslinked network, tri- and tetra-molecular branch points are
two characteristic features whose presence can be inferred indirectly by the
morphology and measured dimensions of the fi brin strands.
58,59
A trimolecu-
lar branch point is mainly a branching of the same protofi bril, whereas a
teteramolecular branch point is a result of two interacting protofi brils.
6.7.3 Platelet recognition
An important physiological function of fi brinogen is its interactions with
circulating platelets through the integrin receptor GPIIb-IIIa on the plate-
let surface, resulting in aggregation and activation of platelets. The binding
to fi brinogen induces conformational changes of GPIIb-IIIa from resting to
activated state.
60-66
From biochemical analysis, the binding affi nity between
fi brinogen and GPIIb-IIIa receptor is much higher in activated state than
