Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 13, Issue 4, Pages 570-579Publisher
WILEY-BLACKWELL
DOI: 10.1111/jth.12785
Keywords
atomic force microscopy; blood coagulation; fibrin; fibrinogen; graphite
Categories
Funding
- Russian Scientific Foundation [14-14-01001, 14-25-00013]
- Russian Science Foundation [14-14-01001] Funding Source: Russian Science Foundation
Ask authors/readers for more resources
BackgroundFibrinogen has been intensively studied with transmission electron microscopy and x-ray diffraction. But until now, a complete 3D structure of the molecule has not yet been available because the two highly flexible C regions could not be resolved in fibrinogen crystals. This study was aimed at determining whether the C regions can be visualized by high-resolution atomic force microscopy. MethodsAtomic force microscopy with super high resolution was used to image single molecules of fibrinogen and fibrin associates. The key approach was to use a graphite surface modified with the monolayer of amphiphilic carbohydrate-glycine molecules and unique supersharp cantilevers with 1nm tip diameter. ResultsFibrinogen C regions were visualized along with the complete domain structure of the protein. In almost all molecules at pH 7.4 the D domain regions had one or two protrusions of average height 0.4 0.1nm and length 21 +/- 6nm. The complex, formed between thrombin and fibrinogen, was also visualized. Images of growing fibrin fibers with clearly visible Cregions have been obtained. ConclusionsFibrin C regions were visible in protofibrils and large fibers; C regions intertwined near a branchpoint and looked like a zipper. These results support the idea that C regions are involved in the thickening of fibrin fibers. In addition, new details were revealed about the behavior of individual fibrin molecules during formation of the fibrin network. Under the diluted condition, the positioning of the C regions could suggest their involvement in long-range interactions between fibrin but not fibrinogen molecules.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available