Properties of DNA- and Protein-Scaffolded Lipid Nanodiscs
Properties of DNA- and Protein-Scaffolded Lipid Nanodiscs
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DOI：
10.1021/acsnano.0c07128
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发表时间：
2021-01-26
期刊：
影响因子：
17.1
通讯作者：
Rothemund, Paul W. K.
中科院分区：
文献类型：
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作者：
Maingi, Vishal;Rothemund, Paul W. K.
天然脂质双层的特性对于许多膜蛋白的调节至关重要。支架纳米盘提供了一个体外脂质双层平台，可在接近天然脂质双层的环境中承载膜蛋白。然而，支架封闭双层的特性可能与本体细胞膜的特性显着不同。因此，为了提高纳米圆盘的实用性，有必要了解受支架限制的脂质的特性。我们使用计算分子动力学和建模方法来了解纳米圆盘尺寸、支架类型（DNA 或蛋白质）和 DNA 支架的疏水修饰对双层稳定性以及封闭双层的性质接近本体双层的程度的影响。关于实现整体双层行为，我们发现DNA支架的电荷中和比其修饰的总疏水含量更重要：具有大量短烷基链的支架的双层特性比具有较少长烷基链的支架更好。此外，DNA支架的完全电荷中和可以实现更好的脂质结合和更稳定的双层，正如测量将支架从脂质双层斑块上移开所需的力的引导分子动力学模拟所显示的那样。综合考虑，我们的模拟为适合研究膜蛋白的 DNA 支架纳米盘的设计提供了指导。
The properties of natural lipid bilayers are vital to the regulation of many membrane proteins. Scaffolded nanodiscs provide an in vitro lipid bilayer platform to host membrane proteins in an environment that approximates native lipid bilayers. However, the properties of scaffold-enclosed bilayers may depart significantly from those of bulk cellular membranes. Therefore, to improve the usefulness of nanodiscs it is essential to understand the properties of lipids restricted by scaffolds. We used computational molecular dynamics and modeling approaches to understand the effects of nanodisc size, scaffold type (DNA or protein), and hydrophobic modification of DNA scaffolds on bilayer stability and degree to which the properties of enclosed bilayers approximate bulk bilayers. With respect to achieving bulk bilayer behavior, we found that charge neutralization of DNA scaffolds was more important than the total hydrophobic content of their modifications: bilayer properties were better for scaffolds having a large number of short alkyl chains than those having fewer long alkyl chains. Further, complete charge neutralization of DNA scaffolds enabled better lipid binding, and more stable bilayers, as shown by steered molecular dynamics simulations that measured the force required to dislodge scaffolds from lipid bilayer patches. Considered together, our simulations provide a guide to the design of DNA-scaffolded nanodiscs suitable for studying membrane proteins.