http://www.cnr.it/ontology/cnr/individuo/prodotto/ID167036
Early events in insulin fibrillization studied by time-lapse atomic force microscopy (Articolo in rivista)
- Type
- Label
- Early events in insulin fibrillization studied by time-lapse atomic force microscopy (Articolo in rivista) (literal)
- Anno
- 2006-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1529/biophysj.105.068833 (literal)
- Alternative label
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Podestà A.; G.Tiana; P. Milani; M. Manno. (literal)
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- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Italian Natl Res Council, Inst Biophys Palermo, I-90146 Palermo, Italy; Univ Milan, Ist Nazl Fis Mat, Dipartimento Fis, Milan, Italy; Univ Milan, Cimaina, Milan, Italy; Ist Nazl Fis Nucl, I-20133 Milan, Italy (literal)
- Titolo
- Early events in insulin fibrillization studied by time-lapse atomic force microscopy (literal)
- Abstract
- The importance of understanding the mechanism of protein aggregation into insoluble amyloid fibrils lies not only in its medical consequences, but also in its more basic properties of self-organization. The discovery that a large number of uncorrelated proteins can form, under proper conditions, structurally similar fibrils has suggested that the underlying mechanism is a general feature of polypeptide chains. In this work, we address the early events preceding amyloid fibril formation in solutions of zinc-free human insulin incubated at low pH and high temperature. Here, we show by time-lapse atomic force microscopy that a steady-state distribution of protein oligomers with a quasiexponential tail is reached within a few minutes after heating. This metastable phase lasts for a few hours, until fibrillar aggregates are observable. Although for such complex systems different aggregation mechanisms can occur simultaneously, our results indicate that the pre fibrillar phase is mainly controlled by a simple coagulation-evaporation kinetic mechanism, in which concentration acts as a critical parameter. These experimental facts, along with the kinetic model used, suggest a critical role for thermal concentration fluctuations in the process of fibril nucleation. (literal)
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