Control of Anti-Thrombogenic Properties: Surface-Induced Self-Assembly of Fibrinogen Fibers

Koo, Jaseung; Galanakis, Dennis K.; Liu, Ying; Ramek, Alexander; Fields, Adam C.; Ba, Xiaolan; Simon, Marcia; Rafailovich, Miriam

doi:10.1021/bm2015976

Cited by 41 publications

(75 citation statements)

References 34 publications

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“…Fibrin formation is triggered by thrombin cleavage of fibrinopeptides on fibrinogen molecules, which allows them to spontaneously self-assemble into large fibers that provide the support structure of the thrombus and promote healing. Many aspects of their structure and functions still remain unknown [37,38]. The distinction between fibrinogen and fibrin is needed for determination of the size and place of thrombus formation.…”

Section: Discussionmentioning

confidence: 99%

Targeting Human Thrombus by Liposomes Modified with Anti-Fibrin Protein Binders

et al. 2019

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Development of tools for direct thrombus imaging represents a key step for diagnosis and treatment of stroke. Nanoliposomal carriers of contrast agents and thrombolytics can be functionalized to target blood thrombi by small protein binders with selectivity for fibrin domains uniquely formed on insoluble fibrin. We employed a highly complex combinatorial library derived from scaffold of 46 amino acid albumin-binding domain (ABD) of streptococcal protein G, and ribosome display, to identify variants recognizing fibrin cloth in human thrombus. We constructed a recombinant target as a stretch of three identical fibrin fragments of 16 amino acid peptide of the Bβ chain fused to TolA protein. Ribosome display selection followed by large-scale Enzyme-Linked ImmunoSorbent Assay (ELISA) screening provided four protein variants preferentially binding to insoluble form of human fibrin. The most specific binder variant D7 was further modified by C-terminal FLAG/His-Tag or double His-tag for the attachment onto the surface of nanoliposomes via metallochelating bond. D7-His-nanoliposomes were tested using in vitro flow model of coronary artery and their binding to fibrin fibers was demonstrated by confocal and electron microscopy. Thus, we present here the concept of fibrin-targeted binders as a platform for functionalization of nanoliposomes in the development of advanced imaging tools and future theranostics.

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Section: Discussionmentioning

confidence: 99%

Targeting Human Thrombus by Liposomes Modified with Anti-Fibrin Protein Binders

et al. 2019

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“…The primary one is through the coagulation cascade, whereby the activation of Hageman factor initiates the intrinsic pathway of clotting, ultimately forming cross‐linked fibrin. A second mechanism results from the ability of hydrophobic surfaces to unfold fibrinogen in a way that allows formation of fibrinogen/fibrin fibers in the absence of thrombin . Loss of endothelial cell lining from the lumen of BVs, via thermal injury, may reveal hydrophobic residues, ultimately resulting in fibrinogen/fibrin fibril formation through the latter mechanism.…”

Section: Discussionmentioning

confidence: 99%

Blood vessel occlusion in peri‐burn tissue is secondary to erythrocyte aggregation and mitigated by a fibronectin‐derived peptide that limits burn injury progression

Asif¹,

Rahim²,

Fenner³

et al. 2016

Wound Repair Regeneration

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Although vascular occlusion has long been noted in peri-burn tissue, the literature is inconsistent regarding the nature of the occlusion, with articles in the 1940s claiming that erythrocytes were the culprit and in the 1980s-1990s that microthrombi were responsible. To better define the nature of vessel occlusion, we studied two porcine burn models, a hot comb horizontal injury model and a vertical injury progression model. In both cases, tissue from the first two days after burn were stained with hemotoxylin and eosin, or probed for platelets or for fibrinogen/fibrin. Erythrocytes, identified as nonstained, clumped, anuclear, 5 µm cells, occluded most blood vessels (BVs) in both burn models. In contrast, platelet or fibrinogen/fibrin antibodies stained BV occlusions minimally at early time points, and only up to 16% of deep dermal BVs at 48 hours in the hot comb model and up to 7% at 24 hours in the vertical injury progression model. Treatment of animals with a fibronectin-derived peptide (P12), which limits burn injury progression and can dilate peripheral microvasculature, reduced erythrocyte occlusion by at least 50%, speeded healing and reduced scarring. Early erythrocyte aggregation, rather than thrombosis, explains the ineffectiveness of anticoagulants to prevent burn injury progression.

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“…The sites of the N‐terminal α ‐chain motif Gly‐Pro‐Arg‐Pro (GPRP), known as knob A, becomes exposed upon the release of FpAs (Koo et al ., ). Knob A is complementary to pocket a, positioned in the γ‐ chains of the D domain of another fibrinogen molecule, resulting in A–a interactions (Figure A).…”

Section: Fibrin Fibre Formation and Its Potential Influence On Fractumentioning

confidence: 97%

Structural properties of fracture haematoma: current status and future clinical implications

Wang

Friis

Glatt

et al. 2016

J Tissue Eng Regen Med

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Blood clots (haematomas) that form immediately following a bone fracture have been shown to be vital for the subsequent healing process. During the clotting process, a number of factors can influence the fibrin clot structure, such as fibrin polymerization, growth factor binding, cellular infiltration (including platelet retraction), protein concentrations and cytokines. The modulation of the fibrin clot structure within the fracture site has important clinical implications and could result in the development of multifunctional scaffolds that mimic the natural structure of a haematoma. Artificial haematoma structures such as these can be created from the patient's own blood and can therefore act as an ideal bone defect filling material for potential clinical application to accelerate bone regeneration. Copyright © 2016 John Wiley & Sons, Ltd.

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Control of Anti-Thrombogenic Properties: Surface-Induced Self-Assembly of Fibrinogen Fibers

Cited by 41 publications

References 34 publications

Targeting Human Thrombus by Liposomes Modified with Anti-Fibrin Protein Binders

Targeting Human Thrombus by Liposomes Modified with Anti-Fibrin Protein Binders

Blood vessel occlusion in peri‐burn tissue is secondary to erythrocyte aggregation and mitigated by a fibronectin‐derived peptide that limits burn injury progression

Structural properties of fracture haematoma: current status and future clinical implications

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