Amyloid-Forming Proteins Alter the Local Mechanical Properties of Lipid Membranes

作者：Burke Kathleen A; Yates Elizabeth A; Legeiter Justin^*

来源：Biochemistry, 2013, 52(5): 808-817.

DOI：10.1021/bi301070v

A diverse number of diseases, including Alzheimer%26apos;s disease, Huntington%26apos;s disease, and type 2 diabetes, are characterized by the formation of fibrillar protein aggregates termed amyloids. The precise mechanism by which aggregates are toxic remains unclear; however, these proteins have been shown to interact strongly with lipid membranes. We investigated morphological and mechanical changes in model lipid bilayers exposed to amyloid-forming proteins by reconstructing the tapping forces associated with atomic force microscopy (AFM) imaging in solution. Tip/sample tapping forces contain information regarding mechanical properties of surfaces. Interpretation of the mechanical changes in the bilayers was aided by numerical simulations of the entire AFM experiment. Amyloid-forming proteins disrupted distinct regions of the bilayer morphology, and these regions were associated with decreased Young%26apos;s modulus and adhesive properties. These changes in bilayer mechanical properties upon exposure to amyloid-forming proteins may represent a common mechanism leading to membrane dysfunction in amyloid diseases.

• 出版日期2013-2-5