title: Amyloid-like aggregates formation by blood plasma fibronectin.
abstract: Fibronectin (FN) is a multifunctional glycoprotein of the extracellular matrix (ECM) playing critical roles in physiological and pathological cell processes like adhesion, migration, growth, and differentiation. These various functions of FN are modulated by its supramolecular state. Indeed, FN can polymerize into different types of assemblies like fibrils and aggregates. However, the mechanism of polymerization and the effects of such assemblies on cell behaviors still remain to be elucidated. Here we show that upon irreversible thermal denaturation, human blood plasma fibronectin forms high molecular weight aggregates. These compact and globular aggregates show amyloid features: they are stabilized by intermolecular b-sheets, they bind Thioflavin T and they are resistant to reducing and denaturing agents. Their characterization by electrospray ionization charge detection mass spectrometry shows that two populations can be distinguished according to the mass and charge density. Despite their amyloid features and the presence of hydrophobic patches on their surface, these aggregates are not toxic for cells. However, their binding abilities to gelatin and RGD are drastically decreased compare to native FN, suggesting possible effects on ECM-cell interactions.
authors.affiliation: ERRMECe, I-MAT FD4122, Université de Cergy-Pontoise, MIR, rue Descartes, 95031, Neuville sur Oise Cedex, France.
authors.forename: Rümeyza
authors.initials: R
authors.lastname: Bascetin
authors.affiliation: ERRMECe, I-MAT FD4122, Université de Cergy-Pontoise, MIR, rue Descartes, 95031, Neuville sur Oise Cedex, France.
authors.forename: Khadija
authors.initials: K
authors.lastname: Admane
authors.affiliation: ERRMECe, I-MAT FD4122, Université de Cergy-Pontoise, MIR, rue Descartes, 95031, Neuville sur Oise Cedex, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Agniel
authors.affiliation: Université Grenoble Alpes, Institut Technologique de Grenoble, CNRS, UMR 5628, LMGP, 3 Parvis Louis Néel, 38016, Grenoble, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Boudou
authors.affiliation: Université Lyon 1-CNRS, Université de Lyon, UMR5306, Institut Lumière Matière, 69622, Villeurbanne, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Doussineau
authors.affiliation: Université Lyon 1-CNRS, Université de Lyon, UMR5306, Institut Lumière Matière, 69622, Villeurbanne, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Antoine
authors.affiliation: ERRMECe, I-MAT FD4122, Université de Cergy-Pontoise, MIR, rue Descartes, 95031, Neuville sur Oise Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gallet
authors.affiliation: ERRMECe, I-MAT FD4122, Université de Cergy-Pontoise, MIR, rue Descartes, 95031, Neuville sur Oise Cedex, France.
authors.forename: Johanne
authors.initials: J
authors.lastname: Leroy-Dudal
authors.affiliation: ERRMECe, I-MAT FD4122, Université de Cergy-Pontoise, MIR, rue Descartes, 95031, Neuville sur Oise Cedex, France. Electronic address: charlotte.vendrely@u-cergy.fr.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vendrely
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000097:blood* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D013696:Temperature
chemical_list: D000682:Amyloid; D005353:Fibronectins
keywords: Aggregates; Human fibronectin; Self-assembly