An Unconventional Fusion Mechanism at the Origin of Eukaryotic Membranes

Abstract

Eukaryogenesis remains one of biology’s most intriguing transitions, yet the eventsdriving the emergence of the eukaryotic cell membrane have not been sufficiently ex-plored. Canonical membrane fusion models, are not appropriate to explain the transi-tion from an archaeal cell membrane to a bacterial one, via heterochiral intermediates.Here, we show that a non-canonical, lipid-mediated mechanism spontaneously generatesclosed bilayers of mixed bacterial and archaeal lipids. Using as a proxy a combinationof enhanced-sampling and unbiased molecular dynamics simulations, we demonstratethat transient edge-mediated archaeal intermediates merge with bacterial vesicles with-out the formation or expansion of a fusion pore. Key indicators include reduced energybarriers and significant membrane stability post-fusion. The edge-induced route bridgesthe inconsistencies found in protocell models and protein-dependent pathways, propos-ing an unconventional explanation that describes how early eukaryotic systems achievedmembrane continuity. These findings provide a plausible biophysical basis for the originof the eukaryotic plasma membrane.