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The relationship between platelet adhesion on surfaces and the structure versus the amount of adsorbed fibrinogen

Paper ID Volume ID Publish Year Pages File Format Full-Text
9905 653 2010 8 PDF Available
Title
The relationship between platelet adhesion on surfaces and the structure versus the amount of adsorbed fibrinogen
Abstract

While platelet adhesion to biomaterial surfaces is widely recognized to be related to adsorbed fibrinogen (Fg), it has remained controversial whether platelet adhesion is in response to the adsorbed amount or the adsorbed conformation of this protein. To address this issue, we designed a series of platelet adhesion studies to clearly separate these two factors, thus enabling us to definitively determine whether it is the amount or the conformation of adsorbed Fg that mediates platelet response. Fg was adsorbed to a broad range of surface chemistries from a wide range of solution concentrations, with the amount and conformation of adsorbed Fg determined by absorbance and circular dichroism (CD) spectropolarimetry, respectively. Platelet adhesion response was determined by lactate dehydrogenase (LDH) assay and scanning electron microscopy (SEM). Our results show that platelet adhesion is strongly correlated with the degree of adsorption-induced unfolding of Fg (r2 = 0.96) with essentially no correlation with the amount of Fg adsorbed (r2 = 0.04). Platelet receptor inhibitor studies using an RGDS peptide reduced platelet adhesion by only about 50%, and SEM results show that adherent platelets after RGDS blocking were much more rounded with minimal extended filopodia compared with the unblocked platelets. These results provide definitive proof that the conformation of adsorbed Fg is the critical determinant of platelet adhesion, not the amount of Fg adsorbed, with adsorption-induced unfolding potentially exposing two distinctly different types of platelet binding sites in Fg; one that induces platelet adhesion alone and one that induces both platelet adhesion and activation.

Keywords
Adsorption; Fibrinogen; Protein adsorption; Platelet adhesion; Haemocompatibility
First Page Preview
The relationship between platelet adhesion on surfaces and the structure versus the amount of adsorbed fibrinogen
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 5, February 2010, Pages 832–839
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering