Spontaneous Lipid Nanodisc Fomation by Amphiphilic Polymethacrylate Copolymers.
Spontaneous Lipid Nanodisc Fomation by Amphiphilic Polymethacrylate Copolymers.
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DOI：
10.1021/jacs.7b10591
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发表时间：
2017-12-27
影响因子：
15
通讯作者：
Ramamoorthy A
中科院分区：
文献类型：
--
作者：
Yasuhara K;Arakida J;Ravula T;Ramadugu SK;Sahoo B;Kikuchi JI;Ramamoorthy A
在不同类型的纳米盘中，对脂质双层的使用越来越感兴趣，基于合成的纳米盘的独特特征在于启用了苯乙烯 - 元素酸（SMA）的含量。基于聚合物的脂质纳米激会受到限制，因为很强吸收芳香族与各种实验测量相互作用。通过脂质的碎片囊泡通过光散射，电子显微镜，差异扫描和溶液和固态NMR实验，我们进一步证明了新开发的聚合物在动力学中的独特应用，用于动力学的结构性和结构性表征我们的结果证明报道的新型无苯乙烯聚合物可用于高通量生物物理实验。
There is a growing interest in the use of lipid bilayer nanodiscs for various biochemical and biomedical applications. Among the different types of nanodiscs, the unique features of synthetic polymer-based nanodiscs have attracted additional interest. A styrene–maleic acid (SMA) copolymer demonstrated to form lipid nanodiscs has been used for structural biology related studies on membrane proteins. However, the application of SMA polymer based lipid nanodiscs is limited because of the strong absorption of the aromatic group interfering with various experimental measurements. Thus, there is considerable interest in the development of other molecular frameworks for the formation of polymer-based lipid nanodiscs. In this study, we report the first synthesis and characterization of a library of polymethacrylate random copolymers as alternatives to SMA polymer. In addition, we experimentally demonstrate the ability of these polymers to form lipid bilayer nanodiscs through the fragmentation of lipid vesicles by means of light scattering, electron microscopy, differential scanning calorimetry, and solution and solid-state NMR experiments. We further demonstrate a unique application of the newly developed polymer for kinetics and structural characterization of the aggregation of human islet amyloid polypeptide (also known as amylin) within the lipid bilayer of the polymer nanodiscs using thioflavin-T-based fluorescence and circular dichroism experiments. Our results demonstrate that the reported new styrene-free polymers can be used in high-throughput biophysical experiments. Therefore, we expect that the new polymer nanodiscs will be valuable in the structural studies of amyloid proteins and membrane proteins by various biophysical techniques.
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