Thaipurayil Madanan Krishnakavya, Li Yuhan, Boide-Trujillo Valeria J, Russell David A, Bonfio Claudia
Institut de Science et d'Ingénierie Supramoléculaires (ISIS), CNRS UMR 7006, University of Strasbourg 8 Allée Gaspard Monge 67000 Strasbourg France
Department of Biochemistry, University of Cambridge Tennis Court Road CB2 1GA Cambridge UK.
Chem Sci. 2024 Oct 29;15(47):19787-19794. doi: 10.1039/d4sc05362a. eCollection 2024 Dec 4.
Biological membranes are composed exclusively of phospholipids comprising glycerol-1-phosphate or glycerol-3-phosphate. By contrast, primitive membranes would have likely been composed of heterogeneous mixtures of phospholipids, including non-natural analogues comprising glycerol-2-phosphate, as delivered by prebiotic synthesis. Thus, it is not clear how the selection of natural phospholipids could have come about. Here we show how differences in supramolecular properties, but not molecular properties, could have driven the selection of natural phosphatidic acids in primitive membranes. First, we demonstrate that at the molecular level it is unlikely that any prebiotic synthesis or hydrolysis pathway would have enabled the selection of natural phosphatidic acids. Second, we report that at the supramolecular level, natural phospholipids display a greater tendency to self-assemble in more packed and rigid membranes than non-natural analogues of the same chain length. Finally, taking advantage of these differences, we highlight that Mg, but not Na, K, Ca or Zn, drives the selective precipitation of non-natural phosphatidic acids from heterogeneous mixtures obtained by prebiotic synthesis, leaving membranes proportionally enriched in natural phosphatidic acids. Our findings delineate a plausible pathway by which the transition towards biological membranes could have occurred under conditions compatible with prebiotic metal-driven processes, such as non-enzymatic RNA polymerization.
生物膜仅由包含甘油-1-磷酸或甘油-3-磷酸的磷脂组成。相比之下，原始膜可能由磷脂的异质混合物组成，包括通过益生元合成产生的包含甘油-2-磷酸的非天然类似物。因此，尚不清楚天然磷脂的选择是如何产生的。在这里，我们展示了超分子性质而非分子性质的差异如何驱动原始膜中天然磷脂酸的选择。首先，我们证明在分子水平上，任何益生元合成或水解途径都不太可能实现天然磷脂酸的选择。其次，我们报告在超分子水平上，与相同链长的非天然类似物相比，天然磷脂在更紧密和刚性的膜中表现出更大的自组装倾向。最后，利用这些差异，我们强调镁而非钠、钾、钙或锌会促使非天然磷脂酸从益生元合成得到的异质混合物中选择性沉淀，从而使膜中天然磷脂酸按比例富集。我们的研究结果描绘了一条合理的途径，在与益生元金属驱动过程（如非酶促RNA聚合）相容的条件下，向生物膜的转变可能由此发生。
