NDLI: A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets

Content Provider	Royal Society of Chemistry (RSC)
Author	Gupta, Anirban Sen Modery-Pawlowski, Christa L. Haji-Valizadeh, Hassan
Copyright Year	2014
Abstract	There is substantial clinical interest in synthetic platelet analogs for potential application in transfusion medicine. To this end, our research is focused on self-assembled peptide–lipid nanoconstructs that can undergo injury site-selective adhesion and subsequently promote site-directed active platelet aggregation, thus mimicking platelet's primary hemostatic actions. For injury site-selective adhesion, we have utilized a coagulation factor FVIII-derived VWF-binding peptide (VBP). FVIII binds to VWF's D′–D3 domain while natural platelet GPIbα binds to VWF's A1 domain. Therefore, we hypothesized that the VBP-decorated nanoconstructs will adhere to VWF without mutual competition with natural platelets. We further hypothesized that the adherent VBP-decorated constructs can enhance platelet aggregation when co-decorated with a fibrinogen-mimetic peptide (FMP). To test these hypotheses, we used glycocalicin to selectively block VWF's A1 domain and, using fluorescence microscopy, studied the binding of fluorescently labeled VBP-decorated nanoconstructs versus platelets to ristocetin-treated VWF. Subsequently, we co-decorated the nanoconstructs with VBP and FMP and incubated them with human platelets to study construct-mediated enhancement of platelet aggregation. Decoration with VBP resulted in substantial construct adhesion to ristocetin-treated VWF even if the A1-domain was blocked by glycocalicin. In comparison, such A1-blocking resulted in significant reduction of platelet adhesion. Without A1-blocking, the VBP-decorated constructs and natural platelets could adhere to VWF concomitantly. Furthermore, the constructs co-decorated with VBP and FMP enhanced active platelet aggregation. The results indicate significant promise in utilizing the FVIII-derived VBP in developing synthetic platelet analogs that do not interfere with VWF-binding of natural platelets but allow site-directed enhancement of platelet aggregation when combined with FMP.
Starting Page	4765
Ending Page	4773
Page Count	9
File Format	HTM / HTML PDF
ISSN	20403364
Volume Number	6
Issue Number	9
Journal	Nanoscale
DOI	10.1039/c3nr06400j
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Platelet Transfusion medicine VBP Site-directed mutagenesis Coagulation FMP Fluorescence microscope Peptide Kripke semantics
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets†

vWf, Platelets, and Megakaryocytes

Adhesion of platelets to human artery subendothelium: effect of factor VIII-von Willebrand factor of various multimeric composition

Adhesion of platelets to human artery subendothelium: effect of factor VIII-von Willebrand factor of various multimeric composition

Influence of Factor VIII-VON Willebrand Factor on Platelet Adhesion to Human Artery Subendothelium in Pulsatile and Non-Pulsatile Flow

Some Immunofluorescent Observations on Factor VIII/von Willebrand Factor in Dogs

Multimeric structure of platelet factor VIII/von Willebrand factor: the presence of larger multimers and their reassociation with thrombin- stimulated platelets

Cleavage of von Willebrand Factor by Granzyme M Destroys Its Factor VIII Binding Capacity

Effect Of The Multimeric Structure Of The Factor VIII/Von Willebrand Factor Protein On Binding To Human Platelets

A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets

Similar Documents

A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets†

vWf, Platelets, and Megakaryocytes

Adhesion of platelets to human artery subendothelium: effect of factor VIII-von Willebrand factor of various multimeric composition

Adhesion of platelets to human artery subendothelium: effect of factor VIII-von Willebrand factor of various multimeric composition

Influence of Factor VIII-VON Willebrand Factor on Platelet Adhesion to Human Artery Subendothelium in Pulsatile and Non-Pulsatile Flow

Some Immunofluorescent Observations on Factor VIII/von Willebrand Factor in Dogs

Multimeric structure of platelet factor VIII/von Willebrand factor: the presence of larger multimers and their reassociation with thrombin- stimulated platelets

Cleavage of von Willebrand Factor by Granzyme M Destroys Its Factor VIII Binding Capacity

Effect Of The Multimeric Structure Of The Factor VIII/Von Willebrand Factor Protein On Binding To Human Platelets

A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets