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【Objectives】Amyloid beta (Aβ) has been implicated in the pathology of Alzheimer's disease (AD). Aβ-peptides are a natively unfolded protein that aggregate into a β-sheet structure of ordered fibrils [1]. This fibril formation proceeds from the assembly of monomers into amorphous aggregates, via proto-fibrils, to produce mature fibrils. Some studies have suggested that these intermediates are the most toxic species. We used cell-sized (>10 μm) model membranes to directly observe spatio-temporal changes in individual vesicles. These biomimetic membranes enable the researcher to manipulate a 'biological' micro-vesicle under
a controlled environment. In this study, we examined the interaction of different oligomeric species of Aβ-40 with a lipid vesicle, observing changes in membrane morphology, in real time using a simple phase-contrast microscope.【Methods】Giant liposomes were prepared using the natural swelling method from a dry lipid film. We incubated 80 μM Aβ-40 in 20 mM Tris, pH 7.4 (Tris) at 37 oC for various periods. Immediately after incubation, Aβ-40 (2μM) was added to cell‐sized lipid vesicles composed of dioleoyl-phosphatidylcholine(DOPC), and their interaction was observed in real‐time [2].【Results and Discussion】We found two significantly different membrane‐transformation pathways (slow membrane dynamics and fast membrane dynamics). We characterized the biophysical mechanisms behind these transformations in terms of the change in inner vesicle volume and surface area.
Interestingly, mature fibrils, which are often considered inert species, also induced profound membrane changes. The real‐time observation of these morphological transformations, which
can be missed in a previous analyses, may help to unlock the mechanisms of AD's Aβ‐induced neuro‐ degeneration [3]. During this symposium, I would like to mention further about our recent resJ. AM. CHEM. SOC. 2010, 132, 10528–10532ults including translocation of Aβ on model membranes [4] and controllable mesoscopic membrane structures [5].