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Visit of Dr. Mattia Rocco

from: Biopolimeri e Proteomica, IRCCSAOU San Martino-IST, Genova, IT 12/10/2015 - 16.30 - Room A51 - DCB

A comprehensive mechanism of fibrin network formation from coupled time-resolved SAXS and multi-angle light scattering

Fibrin network formation is the central event in blood coagulation. It consists basically of two processes: elongation/branching generates an interconnected 3D scaffold of relatively thin fibrils, cooperative lateral aggregation thickens them more than tenfold. The early stages up to the gel point were studied by fast fibrinogen:enzyme mixing experiments using simultaneous SAXS and WA-MALS detection. SAXS data analysis was facilitated by the use of the SAS module of the UltraScan Solution MOdeler (US-SOMO) package. The coupled evolution of the average molecular weight (<M>w), size (<Rg >z), and cross-section (<Rc >z) of the growing fibrils were thus recovered.

They reveal that extended structures, thinner than those predicted by the classic half-staggered, double-stranded mechanism, must quickly form. Extensive modeling suggests an initial phase 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. Some branches in these expanding “lumps” eventually interconnect, forming the pervasive 3D network. While still growing, other branches will then undergo a Ca2+ resulting network filaments, explaining their sudden thickening, low final density, and basic mechanical properties.

REFERENCES

Brookes et al. Fibrinogen species as resolved by HPLC-SAXS data processing within the UltraScan Solution Modeler (US-SOMO) enhanced SAS module. J. Appl. Crystallogr. 2013, 46, 1823−1833.

Rocco et al., A Comprehensive Mechanism of Fibrin Network Formation Involving Early Branching and Delayed Single- to Double-Strand Transition from Coupled Time-Resolved X-ray/Light-Scattering Detection. J. Am. Chem. Soc. 2014, 136:5376–5384. 


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