Learning from Synthetic Models of Extracellular Matrix; Differential Binding of Wild Type and Amyloidogenic Human Apolipoprotein A-I to Hydrogels Formed from Molecules Having Charges Similar to Those Found in Natural GAGs.

ROSU, S. A.; TOLEDO, L; URBANO, B.; SANCHEZ, S. A.; CALABRESE G; TRICERRI, M. A.

PROTEIN JOURNAL

SPRINGER

Año: 2017

1572-3887

Among other components of the extracellularmatrix (ECM), glycoproteins and glycosaminoglycans(GAGs) have been strongly associated to the retention ormisfolding of different proteins inducing the formation ofdeposits in amyloid diseases. The composition of thesemolecules is highly diverse and a key issue seems to be theequilibrium between physiological and pathological events.In order to have a model in which the composition of thematrix could be finely controlled, we designed and synthesizedcrosslinked hydrophilic polymers, the so-calledhydrogels varying the amounts of negative charges andhydroxyl groups that are prevalent in GAGs. We checkedand compared by fluorescence techniques the binding ofhuman apolipoprotein A-I and a natural mutant involved inamyloidosis to the hydrogel scaffolds. Our results indicatethat both proteins are highly retained as long as the negativecharge increases, and in addition it was shown that themutant is more retained than the Wt, indicating that theretention of specific proteins in the ECM could be part ofthe pathogenicity. These results show the importance of theuse of these polymers as a model to get deep insight intothe studies of proteins within macromolecules.