Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, Louisiana 70118, United States.
Biomacromolecules. 2023 Mar 13;24(3):1511-1521. doi: 10.1021/acs.biomac.3c00028. Epub 2023 Feb 21.
Cellular functions of membrane proteins are strongly coupled to their structures and aggregation states in the cellular membrane. Molecular agents that can induce the fragmentation of lipid membranes are highly sought after as they are potentially useful for extracting membrane proteins in their native lipid environment. Toward this goal, we investigated the fragmentation of synthetic liposome using hydrophobe-containing polypeptoids (HCPs), a class of facially amphiphilic pseudo-peptidic polymers. A series of HCPs with varying chain lengths and hydrophobicities have been designed and synthesized. The effects of polymer molecular characteristics on liposome fragmentation are systemically investigated by a combination of light scattering (SLS/DLS) and transmission electron microscopy (cryo-TEM and negative stained TEM) methods. We demonstrate that HCPs with a sufficient chain length (DP ≈ 100) and intermediate hydrophobicity (PNDG mol % = 27%) can most effectively induce the fragmentation of liposomes into colloidally stable nanoscale HCP-lipid complexes owing to the high density of local hydrophobic contact between the HCP polymers and lipid membranes. The HCPs can also effectively induce the fragmentation of bacterial lipid-derived liposomes and erythrocyte ghost cells (i.e., empty erythrocytes) to form nanostructures, highlighting the potential of HCPs as novel macromolecular surfactants toward the application of membrane protein extraction.
膜蛋白的细胞功能与其在细胞膜中的结构和聚集状态密切相关。能够诱导脂质膜碎片化的分子试剂备受关注，因为它们可能有助于在天然脂质环境中提取膜蛋白。为此，我们研究了含有疏水性基团的多肽（HCP）对合成脂质体的碎片化作用，HCP 是一类具有两亲性的假肽聚合物。我们设计并合成了一系列具有不同链长和疏水性的 HCP。通过光散射（SLS/DLS）和透射电子显微镜（冷冻 TEM 和负染 TEM）方法的组合，系统研究了聚合物分子特性对脂质体碎片化的影响。结果表明，具有足够链长（DP ≈ 100）和中等疏水性（PNDG mol % = 27%）的 HCP 最有效地诱导脂质体碎片化，形成胶体稳定的纳米级 HCP-脂质复合物，这归因于 HCP 聚合物与脂质膜之间高密度的局部疏水接触。HCP 还可以有效地诱导细菌脂质衍生的脂质体和红细胞（即空红细胞）的碎片化，形成纳米结构，这突出了 HCP 作为新型大分子表面活性剂在膜蛋白提取中的应用潜力。
