Free Energy of Lipid Bilayer Defects Affected by Alzheimer鈥檚 Disease-Associated Amyloid-尾42 Monomers

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• 作者：Tobias Pobandt ; Volker Knecht
• 刊名：Journal of Physical Chemistry B
• 出版年：2014
• 出版时间：April 3, 2014
• 年：2014
• 卷：118
• 期：13
• 页码：3507-3516
• 全文大小：548K
• 年卷期：v.118,no.13(April 3, 2014)
• ISSN：1520-5207

文摘

Experimental evidence suggests that the amyloid 尾-peptide (A尾) associated with Alzheimer鈥檚 disease strongly disturbs the integrity of lipid bilayers and cell membranes, as a possible origin of the toxicity of this peptide. Here, we have used molecular dynamics simulations to compute the free energy of membrane pores in the presence and absence of A尾. The validation of our approach included the calculation of lipid flip-flop waiting times, which were found to agree well with recent experiments, in contrast with an earlier simulation study that apparently overestimated these waiting times. We find that, compared with peptide-free lipid bilayers, attached A尾₄₂ peptides (i) increase the order parameters of the lipid tails but (ii) decrease the effective width of the hydrophobic region, (iii) reduce the free energy and thus enlarge the density of membrane pores, and (iv) increase the lifetime of pores. A detailed understanding of the interaction of A尾₄₂ with lipid bilayer membranes may assist in the design of therapeutical strategies against Alzheimer鈥檚 disease.