Temperature and pressure tuneable swollen bicontinuous cubic phases approaching nature's length scales

Temperature and pressure tuneable swollen bicontinuous cubic phases approaching nature's length scales
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DOI:
10.1039/c4sm02343a
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发表时间:
2015-01-01
期刊:
影响因子:
3.4
通讯作者:
Brooks, N. J.
Brooks, N. J.
中科院分区:
化学2区
文献类型:
--
作者:
Barriga, H. M. G.;Tyler, A. I. I.;Brooks, N. J.

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双连续立方结构在从蛋白质结晶到药物输送系统的应用中提供了巨大的潜力,并且已经在细胞膜结构中观察到。目前理解和利用这些结构的瓶颈之一是体外产生的立方支架的尺寸比在生物系统中观察到的小得多,在某些情况下相差几乎一个数量级。我们已经解决了这一技术瓶颈,并开发了一种能够制造高度膨胀的双连续立方膜的方法,其长度尺度接近体内可见的长度尺度。至关重要的是,这些立方系统不需要蛋白质的存在。我们已经生成了高度膨胀的 Im3m 对称双连续立方相,其晶格参数高达 480 埃,由单油酸甘油酯、胆固醇和带负电的脂质(DOPS 或 DOPG)的三元混合物组成,并且我们已经能够调整它们的晶格参数。膨胀的立方相对温度和压力高度敏感;这些结构变化可能是通过脂质头基排斥和烃链区域侧向压力之间的精细平衡来控制的。
Bicontinuous cubic structures offer enormous potential in applications ranging from protein crystallisation to drug delivery systems and have been observed in cellular membrane structures. One of the current bottlenecks in understanding and exploiting these structures is that cubic scaffolds produced in vitro are considerably smaller in size than those observed in biological systems, differing by almost an order of magnitude in some cases. We have addressed this technological bottleneck and developed a methodology capable of manufacturing highly swollen bicontinuous cubic membranes with length scales approaching those seen in vivo. Crucially, these cubic systems do not require the presence of proteins. We have generated highly swollen Im3m symmetry bicontinuous cubic phases with lattice parameters of up to 480 angstrom, composed of ternary mixtures of monoolein, cholesterol and negatively charged lipid (DOPS or DOPG) and we have been able to tune their lattice parameters. The swollen cubic phases are highly sensitive to both temperature and pressure; these structural changes are likely to be controlled by a fine balance between lipid headgroup repulsions and lateral pressure in the hydrocarbon chain region.