Institute of Chemistry, Physical Chemistry - Complex Self-Organizing Systems, Martin Luther University (MLU) Halle-Wittenberg, Von-Danckelmann-Platz 4, 06120 Halle (Saale), Germany; Interdisciplinary Research Center HALOmem, Charles Tanford Protein Center, MLU Halle-Wittenberg, Kurt-Mothes-Str. 3a, 06120 Halle (Saale), Germany.
Institute of Chemistry, Physical Chemistry - Complex Self-Organizing Systems, Martin Luther University (MLU) Halle-Wittenberg, Von-Danckelmann-Platz 4, 06120 Halle (Saale), Germany; Department of Chemistry - Molecular Sciences Research Hub, Imperial College London, 82 Wood Ln, W12 0BZ London, United Kingdom.
Biochim Biophys Acta Biomembr. 2021 Oct 1;1863(10):183681. doi: 10.1016/j.bbamem.2021.183681. Epub 2021 Jun 26.
With this study we aim at comparing the well-known lipid membrane model system of liposomes and polymer-encapsulated nanodiscs regarding their lipid properties. Using differential scanning calorimetry (DSC) and continuous-wave electron paramagnetic resonance (CW EPR) spectroscopy, we characterize the temperature-dependent lipid behavior within 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes and nanodiscs made from such liposomes by application of various polymers based on styrene-co-maleic acid (SMA), diisobutylene-alt-maleic acid (DIBMA), and styrene-co-maleic amide sulfobetaine (SMA-SB), a new SMA-derived copolymer containing sulfobetaine side chains. By incorporating a spin label doxyl moiety into the lipid bilayer in position 16 or 5 we were able to study the micropolarity as well as rotational restrictions onto the lipids in the apolar bilayer center and the chain region adjacent to the carbonyl groups, respectively. Our results suggest that all polymers broaden the main melting transition of DMPC, change the water accessibility within the lipid bilayer, and exhibit additional constraints onto the lipids. Independent of the used polymer, the rotational mobility of both spin-labeled lipids decreased with DIBMA exerting less restraints probably due to its aliphatic side chains. Our findings imply that the choice of the solubilizing polymer has to be considered an important step to form lipid nanodiscs which should be included into research of lipid membranes and membrane proteins in the future.
本研究旨在比较脂质体和聚合物包封纳米盘这两种众所周知的脂质膜模型系统，以研究它们的脂质性质。通过使用差示扫描量热法（DSC）和连续波电子顺磁共振（CW EPR）光谱，我们对 1,2-二肉豆蔻酰基-sn-甘油-3-磷酸胆碱（DMPC）脂质体和由这些脂质体制备的纳米盘在温度依赖性脂质行为进行了表征，使用了基于苯乙烯-马来酸（SMA）、异丁烯-马来酸（DIBMA）和苯乙烯-马来酰胺磺基甜菜碱（SMA-SB）的各种聚合物，SMA-SB 是一种含有磺基甜菜碱侧链的新型 SMA 衍生共聚物。通过将自旋标记物 doxyl 部分引入到脂质双层的 16 位或 5 位位置，我们能够分别研究非极性双层中心和靠近羰基的链区的脂质微极性和旋转限制。我们的结果表明，所有聚合物都拓宽了 DMPC 的主要熔融转变，改变了脂质双层内的水可及性，并对脂质产生了额外的限制。无论使用哪种聚合物，两种自旋标记脂质的旋转流动性都随着 DIBMA 的降低而降低，这可能是由于其脂肪侧链的存在。我们的发现意味着选择增溶聚合物是形成脂质纳米盘的重要步骤，这在未来的脂质膜和膜蛋白研究中应予以考虑。
