High-throughput screening of drug-lipid membrane interactions via counter-propagating second harmonic generation imaging.
High-throughput screening of drug-lipid membrane interactions via counter-propagating second harmonic generation imaging.
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DOI：
10.1021/ac2009614
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发表时间：
2011-08-01
影响因子：
7.4
通讯作者：
Conboy, John C.
中科院分区：
文献类型：
--
作者：
Nguyen, Trang T.;Conboy, John C.
在这里，我们报告了使用反传播二次谐波产生（SHG）以无标记的方式成像局部麻醉剂丁卡因与多组分平面支撑脂质双分子层阵列之间的相互作用。脂质双分子层阵列是用3D连续流动微点仪制备的，可以同时检测脂质相和胆固醇含量对丁卡因结合的影响。SHG图像显示，丁卡因对液晶相脂质的结合亲和力高于固凝胶相脂质的结合亲和力。28 mol %胆固醇的存在降低了丁卡因与混合链脂、1-甾醇-2-油基- cn -甘油基-3-胆碱（SOPC）和饱和脂质1,2-二肉豆蔻酰基- cn -甘油基-3-胆碱（DPPC）组成的双层的结合亲和力，而对二不饱和的1,2-二油基- cn -甘油基-3-胆碱（DOPC）没有影响。丁卡因的最大表面过剩量随着磷脂不饱和程度的增加而增加，随着脂质双层中胆固醇的减少而减少。本文证明了SHG成像是一种灵敏的技术，可以直接成像和定量测量药物与多组分脂质双分子层阵列的关联，为评估药物-膜相互作用提供了高通量手段。
Here we report the use of counter-propagating second harmonic generation (SHG) to image the interactions between the local anesthetic tetracaine and a multi-component planar supported lipid bilayer array in a label-free manner. The lipid bilayer arrays, prepared using a 3D continuous flow microspotter, allow the effects of lipid phase and cholesterol content on tetracaine binding to be examined simultaneously. SHG images show that tetracaine has a higher binding affinity to liquid-crystalline phase lipids than to solid-gel phase lipids. The presence of 28 mol % cholesterol decreased the binding affinity of tetracaine to bilayers composed of the mixed chain lipid, 1-steroyl-2-oleoyl-sn-glycero-3-phophocholine (SOPC) and the saturated lipids 1,2-dimyristoyl-sn-glycero-3-phophocholine (DMPC) and 1,2-dipamitoyl-sn-glycero-3-phophocholine (DPPC) while having no effect on di-unsaturated 1,2-dioleoyl-sn-glycero-3-phophocholine (DOPC). The maximum surface excess of tetracaine increases with the degree of unsaturation of the phospholipids and decreases with cholesterol in the lipid bilayers. The paper demonstrates that SHG imaging is a sensitive technique that can directly image and quantitatively measure the association of a drug to a multi-component lipid bilayer array, providing a high-throughput means to assess drug-membrane interactions.
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影响因子：
3.9
作者：
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