Embedding A beta 42 in Heterogeneous Membranes Depends on Cholesterol Asymmetries

作者：Liguori Nicoletta; Nerenberg Paul S; Head Gordon Teresa^*

来源：Biophysical Journal, 2013, 105(4): 899-910.

DOI：10.1016/j.bpj.2013.06.046

Using a coarse-grained lipid and peptide model, we show that the free energy stabilization of amyloid-beta in heterogeneous lipid membranes is predicted to have a dependence on asymmetric distributions of cholesterol compositions across the membrane leaflets. We find that a highly asymmetric cholesterol distribution that is depleted on the exofacial leaflet but enhanced on the cytofacial leaflet of the model lipid membrane thermodynamically favors membrane retention of a fully embedded A beta peptide. However, in the case of cholesterol redistribution that increases concentration of cholesterol on the exofacial layer, typical of aging or Alzheimer%26apos;s disease, the free energy favors peptide extrusion of the highly reactive N-terminus into the extracellular space that may be vulnerable to aggregation, oligomerization, or deleterious oxidative reactivity.

• 出版日期2013-8-20