Fracassi Alessandro, Seoane Andrés, Brea Roberto J, Lee Hong-Guen, Harjung Alexander, Devaraj Neal K
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
Bioinspired Nanochemistry (BioNanoChem) Group, CICA Centro Interdisciplinar de Química e Bioloxía, Universidade da Coruña, A Coruña, Spain.
Nat Chem. 2025 May 22. doi: 10.1038/s41557-025-01829-5.
The plasticity of living cell membranes relies on complex metabolic networks fueled by cellular energy. These metabolic processes exert direct control over membrane properties such as lipid composition and morphological plasticity, which are essential for cellular functions. Despite notable progress in the development of artificial systems mimicking natural membranes, the realization of synthetic membranes capable of sustaining metabolic cycles remains a challenge. Here we present an abiotic phospholipid metabolic network that generates and maintains dynamic artificial cell membranes. Chemical coupling agents drive the in situ synthesis of transiently stable non-canonical phospholipids, leading to the formation and maintenance of phospholipid membranes. We find that phospholipid metabolic cycles can drive lipid self-selection, favouring the enrichment of specific lipid species. Moreover, we demonstrate that controlling lipid metabolism can induce reversible membrane phase transitions, facilitating lipid mixing between distinct populations of artificial membranes. Our work demonstrates that a simple lipid metabolic network can drive dynamic behaviour in artificial membranes, offering insights into mechanisms for engineering functional synthetic compartments.
活细胞膜的可塑性依赖于由细胞能量驱动的复杂代谢网络。这些代谢过程直接控制膜的性质，如脂质组成和形态可塑性，而这些对于细胞功能至关重要。尽管在模仿天然膜的人工系统开发方面取得了显著进展，但实现能够维持代谢循环的合成膜仍然是一项挑战。在此，我们展示了一个非生物磷脂代谢网络，它能生成并维持动态人工细胞膜。化学偶联剂驱动瞬时稳定的非经典磷脂的原位合成，从而导致磷脂膜的形成和维持。我们发现磷脂代谢循环可以驱动脂质的自我选择，有利于特定脂质种类的富集。此外，我们证明控制脂质代谢可以诱导可逆的膜相变，促进不同群体的人工膜之间的脂质混合。我们的工作表明，一个简单的脂质代谢网络可以驱动人工膜中的动态行为，为工程化功能性合成隔室的机制提供了见解。
