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It is well established that amyloid β-protein (Aβ) self-assembly is involved in triggering of Alzheimer's disease. On the other hand, evidence of physiological function of Aβ interacting with lipids has only begun to emerge. Details of Aβ–lipid interactions, which may underlie physiological and pathological activities of Aβ, are not well understood. Here, the effects of salt and 1,2-dimyristoyl- sn-glycero -3-phosphocholine (DMPC) lipids on conformational dynamics of Aβ42 monomer in water are examined by all-atom molecular dynamics (MD). We acquired six sets of 250 ns long MD trajectories for each of the three lipid concentrations (0, 27, and 109 mM) in the absence and presence of 150 mM salt. Ten replica trajectories per set are used to enhance sampling of Aβ42 conformational space. We show that salt facilitates long-range tertiary contacts in Aβ42, resulting in more compact Aβ42 conformations. By contrast, addition of lipids results in lipid-concentration dependent Aβ42 unfolding concomitant with enhanced stability of the turn in the A21–A30 region. At the high lipid concentration, salt enables the N-terminal region of Aβ42 to form long-range tertiary contacts and interact with lipids, which results in formation of a parallel β-strand. Aβ42 forms stable lipid–protein complexes whereby the protein is adhered to the lipid cluster rather than embedded into it. We propose that the inability of Aβ42 monomer to get embedded into the lipid cluster may be important for facilitating repair of leaks in the blood-brain barrier without penetrating and damaging cellular membranes.