Nanoscale Structure and Dynamics of Model Membrane Lipid Raft Systems, Studied by Neutron Scattering Methods
Nanoscale Structure and Dynamics of Model Membrane Lipid Raft Systems, Studied by Neutron Scattering Methods
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DOI：
10.3389/fphy.2022.864746
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发表时间：
2022-04-27
影响因子：
3.1
通讯作者：
Foglia, Fabrizia
中科院分区：
文献类型：
--
作者：
Ahmadi, Delaram;Thompson, Katherine C.;Foglia, Fabrizia
准弹性中子散射（QENS）和小角中子散射（SANS）结合同位素对比度变化，已被用于确定囊泡形式的三组分脂质膜的结构和动力学，所述囊泡形式包含不饱和[棕榈酰-油酰-磷脂酰胆碱（POPC）或二油酰-磷脂酰胆碱（DOPC）]，一种饱和磷脂（二棕榈酰-磷脂酰胆碱（DPPC））和胆固醇作为温度和组成的函数。SANS研究表明，当温度从308 K降至297 K时，由1：1：1摩尔比的DPPC：DOPC：胆固醇和2：2：1摩尔比的DPPC：POPC：胆固醇组成的囊泡膜相分离，分别形成直径约为18 nm和约为7 nm的脂筏。相分离是可逆的温度升高。在含有DOPC的系统中观察到的较大筏归因于DOPC和DPPC之间的脂质烷基链中的较大错配，而不是POPC和DPPC。在283- 323 K温度范围内的QENS研究表明，所得数据最好由两个洛伦兹函数建模：一个窄分量，描述“面内”脂质扩散，和一个更宽的分量，描述脂质烷基链段松弛。整体的“面内”扩散被发现显示出显着的减少时，温度升高，由于囊泡膜从一个包含筏过渡到一个组分脂质均匀混合。使用不同的同位素组合允许测量的面内扩散的总体减少被理解为饱和DPPC脂质的扩散增加和不饱和DOPC/POPC脂质的扩散的相应减少。由于筏被认为主要由饱和脂质和胆固醇组成，筏的分解降低了DPPC对胆固醇的暴露，同时增加了胆固醇对不饱和脂质的暴露。这些结果表明，脂质扩散的敏感性，局部胆固醇浓度，并考虑当地的重要性，而不是膜的全球组成时，了解膜内的脂质扩散过程。SANS和QENS的新组合允许一种非侵入性的方法来表征发生在相分离的模型膜中的结构和动力学，所述相分离的模型膜被设计为模仿在细胞膜中看到的脂质的横向异质性-异质性可以具有病理后果。
Quasi-elastic neutron scattering (QENS) and small angle neutron scattering (SANS), in combination with isotopic contrast variation, have been used to determine the structure and dynamics of three-component lipid membranes, in the form of vesicles, comprising an unsaturated [palmitoyl-oleoyl-phosphatidylcholine (POPC) or dioleoyl-phosphatidylcholine (DOPC)], a saturated phospholipid (dipalmitoyl-phosphatidylcholine (DPPC)), and cholesterol, as a function temperature and composition. SANS studies showed vesicle membranes composed of a 1:1:1 molar ratio of DPPC:DOPC:cholesterol and a 2:2:1 molar ratio of DPPC:POPC:cholesterol phase separated, forming lipid rafts of similar to 18 and similar to 7 nm diameter respectively, when decreasing temperature from 308 to 297 K. Phase separation was reversible upon increasing temperature. The larger rafts observed in systems containing DOPC are attributed to the greater mis-match in lipid alkyl chains between DOPC and DPPC, than for POPC and DPPC. QENS studies, over the temperature range 283-323K, showed that the resulting data were best modelled by two Lorentzian functions: a narrow component, describing the "in-plane" lipid diffusion, and a broader component, describing the lipid alkyl chain segmental relaxation. The overall "in-plane" diffusion was found to show a significant reduction upon increasing temperature due to the vesicle membranes transitioning from one containing rafts to one where the component lipids are homogeneously mixed. The use of different isotopic combinations allowed the measured overall reduction of in-plane diffusion to be understood in terms of an increase in diffusion of the saturated DPPC lipid and a corresponding decrease in diffusion of the unsaturated DOPC/POPC lipid. As the rafts are considered to be composed principally of saturated lipid and cholesterol, the breakdown of rafts decreases the exposure of the DPPC to cholesterol whilst increasing the exposure of cholesterol to unsaturated lipid. These results show the sensitivity of lipid diffusion to local cholesterol concentration, and the importance of considering the local, rather that the global composition of a membrane when understanding the diffusion processes of lipids within the membrane. The novel combination of SANS and QENS allows a non-intrusive approach to characterize the structure and dynamics occurring in phase-separated model membranes which are designed to mimic the lateral heterogeneity of lipids seen in cellular membranes-a heterogeneity that can have pathological consequences.