Solid-to-Liposome Conformational Transition of Phosphatidylcholine and Phosphatidylserine Probed by Atomic Force Microscopy, Infrared Spectroscopy, and Density Functional Theory Calculations.
Solid-to-Liposome Conformational Transition of Phosphatidylcholine and Phosphatidylserine Probed by Atomic Force Microscopy, Infrared Spectroscopy, and Density Functional Theory Calculations.
复制标题
原子力显微镜、红外光谱和密度泛函理论计算探索磷脂酰胆碱和磷脂酰丝氨酸的固体至脂质体构象转变。
DOI：
10.1021/acs.analchem.2c03061
复制
发表时间：
2022-09-27
影响因子：
7.4
通讯作者：
Kurouski, Dmitry
中科院分区：
文献类型：
--
作者：
Dou, Tianyi;Zens, Clara;Schroeder, Katrin;Jiang, Yuan;Makarov, Alexey A.;Kupfer, Stephan;Kurouski, Dmitry
脂质体是用于化疗药物的位点特异性递送的新兴治疗制剂。通过这些载体的药物递送的效率和选择性在很大程度上依赖于它们的表面性质、形状和尺寸。有一个不断增长的需求，分析方法，可用于在单囊泡水平的脂质体的结构和形态表征。AFM-IR是一种结合了扫描探针显微镜和红外光谱学优点的现代光学纳米技术。我们的研究结果表明，AFM-IR可用于探测磷脂组装成脂质体后发生的构象变化。这样的结论可以基于脂质振动带的强度的相应变化，作为分子从固态转变成大的单层囊泡（LUV）。这种光谱分析的LUV形成与密度泛函理论计算还揭示了在何种程度上的分子构象和局部环境的官能团改变AFM-IR光谱的磷脂。使用蜂毒肽作为测试蛋白，我们还检查了LUV可用于蛋白质内化的程度。我们发现蜂毒肽几乎是瞬间进入LUV的，这可以保护它免受环境变化引起的可能的结构改变。这项基础性工作使AFM-IR分析脂质体成为可能，并为确定脂质体-药物相互作用的分子机制开辟了新的途径。
Liposomes are emerging therapeutic formulations for site-specific delivery of chemotherapeutic drugs. The efficiency and selectivity of drug delivery by these carriers largely rely on their surface properties, shape, and size. There is a growing demand for analytical approaches that can be used for structural and morphological characterization of liposomes at the single-vesicle level. AFM-IR is a modern optical nanoscopic technique that combines the advantages of scanning probe microscopy and infrared spectroscopy. Our findings show that AFM-IR can be used to probe conformational changes in phospholipids that take place upon their assembly into liposomes. Such conclusions can be made based on the corresponding changes in intensities of the lipid vibrational bands as the molecules transition from a solid state into large unilamellar vesicles (LUVs). This spectroscopic analysis of LUV formation together with density functional theory calculations also reveals the extent to which the molecular conformation and local environment of the functional groups alter the AFM-IR spectra of phospholipids. Using melittin as a test protein, we also examined the extent to which LUVs can be used for protein internalization. We found that melittin enters LUVs nearly instantaneously, which protects it from possible structural modifications that are caused by a changing environment. This foundational work empowers AFM-IR analysis of liposomes and opens new avenues for determination of the molecular mechanisms of liposome—drug interactions.
登录
查看更多内容
影响因子：
5.7
作者：
Rizevsky, Stanislav;Matveyenka, Mikhail;Kurouski, Dmitry
通讯作者：
Kurouski, Dmitry
影响因子：
5
作者：
Dou, Tianyi;Kurouski, Dmitry
通讯作者：
Kurouski, Dmitry
影响因子：
5.4
作者：
Bulbake U;Doppalapudi S;Kommineni N;Khan W
通讯作者：
Khan W
DOI：
10.1146/annurev-anchem-071114-040435
发表时间：
2015-01-01
期刊：
ANNUAL REVIEW OF ANALYTICAL CHEMISTRY, VOL 8
影响因子：
--
作者：
Centrone, Andrea
通讯作者：
Centrone, Andrea
影响因子：
3.4
作者：
Kreutzberger, Mark A.;Tejada, Emmanuel;Almeida, Paulo F.
通讯作者：
Almeida, Paulo F.