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磷脂双层纳米盘的静态和动态特性

Static and dynamic properties of phospholipid bilayer nanodiscs.

作者信息

Nakano Minoru, Fukuda Masakazu, Kudo Takayuki, Miyazaki Masakazu, Wada Yusuke, Matsuzaki Naoya, Endo Hitoshi, Handa Tetsurou

机构信息

Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.

出版信息

J Am Chem Soc. 2009 Jun 17;131(23):8308-12. doi: 10.1021/ja9017013.

Abstract

Nanodiscs are phospholipid-protein complexes which are relevant to nascent high-density lipoprotein and are applicable as a drug carrier and a tool to immobilize membrane proteins. We evaluated the structure and dynamics of the nanoparticles consisting of dimyristoylphosphatidylcholine (DMPC) and apolipoprotein A-I (apoA-I) with small-angle neutron scattering (SANS) and fluorescence methods and compared them with static/dynamic properties for large unilamellar vesicles. SANS revealed that the nanodisc includes a lipid bilayer with a thickness of 44 A and a radius of 37 A, in which each lipid occupies a smaller area than the reported molecular area of DMPC in vesicles. Fluorescence measurements suggested that DMPC possesses a lower entropy in nanodiscs than in vesicles, because apoA-I molecules, which surround the bilayer, force closer lipid packing, but allow water penetration to the acyl chain ends. Time-resolved SANS experiments revealed that nanodiscs represent a 20-fold higher lipid transfer via an entropically favorable process. The results put forward a conjunction of static/dynamic properties of nanodiscs, where the entropic constraints are responsible for the accelerated desorption of lipids.

摘要

纳米盘是与新生高密度脂蛋白相关的磷脂 - 蛋白质复合物,可用作药物载体和固定膜蛋白的工具。我们用小角中子散射(SANS)和荧光方法评估了由二肉豆蔻酰磷脂酰胆碱(DMPC)和载脂蛋白A - I(apoA - I)组成的纳米颗粒的结构和动力学,并将其与大单层囊泡的静态/动态特性进行了比较。SANS显示纳米盘包含一个厚度为44 Å、半径为37 Å的脂质双层,其中每个脂质占据的面积比报道的囊泡中DMPC的分子面积小。荧光测量表明,DMPC在纳米盘中的熵低于在囊泡中的熵,因为围绕双层的apoA - I分子迫使脂质更紧密地堆积,但允许水渗透到酰基链末端。时间分辨SANS实验表明,纳米盘通过一个熵有利的过程表现出高20倍的脂质转移。结果提出了纳米盘静态/动态特性的结合,其中熵约束是脂质加速解吸的原因。

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