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|Título:||Atomic force microscopy-based molecular recognition of a fibrinogen receptor on human erythrocytes|
|Autor:||Carvalho, Filomena A.|
Pereira, Sónia Vale
Ariëns, Robert A. S.
Santos, Nuno C.
|Editora:||American Chemical Society|
|Citação:||ACS nano VOL. 4 ▪ NO. 8 ▪ 4609–4620 ▪ 2010|
|Resumo:||The established hypothesis for the increase on erythrocyte aggregation associated with a higher incidence of cardiovascular pathologies is based on an increase on plasma adhesion proteins concentration, particularly fibrinogen. Fibrinogen-induced erythrocyte aggregation has been considered to be caused by its nonspecific binding to erythrocyte membranes. In contrast, platelets are known to have a fibrinogen integrin receptor expressed on the membrane surface (the membrane glycoprotein complex αIIbβ3). We demonstrate, by force spectroscopy measurements using an atomic force microscope (AFM), the existence of a single molecule interaction between fibrinogen and an unknown receptor on the erythrocyte membrane, with a lower but comparable affinity relative to platelet binding (average fibrinogen-erythrocyte and-platelet average (un)binding forces were 79 and 97 pN, respectively). This receptor is not as strongly influenced by calcium and eptifibatide (an αIIbβ3 specific inhibitor) as the platelet receptor. However, its inhibition by eptifibatide indicates that it is an αIIbβ3-related integrin. Results obtained for a Glanzmann thrombastenia (a rare hereditary bleeding disease caused by αIIbβ3 deficiency) patient show (for the first time) an impaired fibrinogen-erythrocyte binding. Correlation with genetic sequencing data demonstrates that one of the units of the fibrinogen receptor on erythrocytes is a product of the expression of the β3 gene, found to be mutated in this patient. This work demonstrates and validates the applicability of AFM-based force spectroscopy as a highly sensitive, rapid and low operation cost nanotool for the diagnostic of genetic mutations resulting in hematological diseases, with an unbiased functional evaluation of their severity.|
|Descrição:||© 2010 American Chemical Society|
|Aparece nas colecções:||IMM - Artigos em Revistas Internacionais|
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