کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1959509 1057940 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Early Events in Insulin Fibrillization Studied by Time-Lapse Atomic Force Microscopy
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Early Events in Insulin Fibrillization Studied by Time-Lapse Atomic Force Microscopy
چکیده انگلیسی

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 prefibrillar 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 90, Issue 2, 15 January 2006, Pages 589–597
نویسندگان
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