Nakano Minoru, Fukuda Masakazu, Kudo Takayuki, Miyazaki Masakazu, Wada Yusuke, Matsuzaki Naoya, Endo Hitoshi, Handa Tetsurou
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
J Am Chem Soc. 2009 Jun 17;131(23):8308-12. doi: 10.1021/ja9017013.
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.
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。
