Unconventional Fusion Mechanism at the Origin of Eukaryotic Membranes

Eukaryogenesis remains one of biology’s most intriguing transitions, yet the events driving the emergence of the eukaryotic cell membrane have not been sufficiently explored. Canonical membrane fusion models, are not appropriate to explain the transition from an archaeal cell membrane to a bacterial one, via heterochiral intermediates. Here, we show that a non-canonical, lipid-mediated mechanism spontaneously generates closed bilayers of mixed bacterial and archaeal lipids. Using as a proxy a combination of enhanced-sampling and unbiased molecular dynamics simulations, we demonstrate that transient edge-mediated archaeal intermediates merge with bacterial vesicles without the formation or expansion of a fusion pore. Key indicators include reduced energy barriers and significant membrane stability post-fusion. The edge-induced route bridges the inconsistencies found in protocell models and protein-dependent pathways, proposing an unconventional explanation that describes how early eukaryotic systems achieved membrane continuity. These findings provide a plausible biophysical basis for the origin of the eukaryotic plasma membrane.