title: PlA2 Polymorphism in Glycoprotein IIb/IIIa Modulates the Morphology and Nanomechanics of Platelets.
abstract: Glycoprotein IIb/IIIa (GPIIb/IIIa) is the most abundant platelet surface receptor for fibrinogen and von Willebrand factor. Polymorphism PlA1/A2 in the gene of GPIIb/IIIa is among the risk factors for the development of arterial and venous thrombosis. The aim of this study is to evaluate the effect of the carriage of PlA1/A2 on the size, topographic features, and membrane stiffness of platelets from healthy controls and patients with deep venous thrombosis (DVT). Atomic force microscopy (AFM) imaging and nanoindentation (force-distance curves) were applied to investigate the morphological and nanomechanical properties (Young's modulus) of platelets immobilized on glass surface. The surface roughness ( Ra) and height ( h) of platelets from patients with DVT, carriers of mutant allele PlA2 ( Ra= 30.2 ± 6 nm; h = 766 ± 182 nm) and noncarriers ( Ra= 28.6 ± 6 nm; h = 865 ± 290 nm), were lower than those of healthy carriers of allele PlA2 ( Ra= 48.1 ± 12 nm; h = 1072 ± 338 nm) and healthy noncarriers ( Ra= 49.7 ± 14 nm; h = 1021 ± 433 nm), respectively. Platelets isolated from patients with DVT, both carriers and noncarriers, exhibit much higher degree of stiffness at the stage of spreading ( E = 327 ± 85 kPa and 341 ± 102 kPa, respectively) compared to healthy noncarriers ( E = 198 ± 50 kPa). In addition, more pronounced level of platelet activation was found in polymorphism carriers. In conclusion, the carriage of PlA2 allele modulates the activation state, morphology, and membrane elasticity of platelets.
authors.affiliation: 1 Department of Biomacromolecules and Biomolecular Interactions, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Svetla
authors.initials: S
authors.lastname: Todinova
authors.affiliation: 2 Department of Biochemistry, Medical University, Pleven, Bulgaria.
authors.forename: Regina
authors.initials: R
authors.lastname: Komsa-Penkova
authors.affiliation: 1 Department of Biomacromolecules and Biomolecular Interactions, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Sashka
authors.initials: S
authors.lastname: Krumova
authors.affiliation: 1 Department of Biomacromolecules and Biomolecular Interactions, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Stefka G
authors.initials: SG
authors.lastname: Taneva
authors.affiliation: 2 Department of Biochemistry, Medical University, Pleven, Bulgaria.
authors.forename: Georgy
authors.initials: G
authors.lastname: Golemanov
authors.affiliation: 2 Department of Biochemistry, Medical University, Pleven, Bulgaria.
authors.forename: Galia
authors.initials: G
authors.lastname: Georgieva
authors.affiliation: 3 Department of Surgery, University Hospital, Pleven, Bulgaria.
authors.forename: Pencho
authors.initials: P
authors.lastname: Tonchev
authors.affiliation: 3 Department of Surgery, University Hospital, Pleven, Bulgaria.
authors.forename: Boris
authors.initials: B
authors.lastname: Tsankov
authors.affiliation: 3 Department of Surgery, University Hospital, Pleven, Bulgaria.
authors.forename: Lyubomir
authors.initials: L
authors.lastname: Beshev
authors.affiliation: 4 Department of Physical Chemistry, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Balashev
authors.affiliation: 1 Department of Biomacromolecules and Biomolecular Interactions, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Tonya D
authors.initials: TD
authors.lastname: Andreeva
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D055119:Elastic Modulus; D005260:Female; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D008297:Male; D018625:Microscopy, Atomic Force; D008875:Middle Aged; D040201:Platelet Membrane Glycoprotein IIb / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D020246:Venous Thrombosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C061248:ITGB3 protein, human; D039661:Integrin beta3; D040201:Platelet Membrane Glycoprotein IIb
keywords: Young’s modulus; atomic force microscopy; deep venous thrombosis; platelets morphology; polymorphism in glycoprotein IIb/IIIa