Organocatalyzed Bottom-up Formation of Protocells

The organisation of living biological systems into cellular structures is a characteristic that enables differentiation from the environment. ¹ It is assumed that a pivotal step in the development of life is compartmentalization, achieved through the formation of vesicle-like structures. Fatty acids ^{2-3 [i] 4} - or phospholipids ⁵ - have been used to simulate prebiotic vesicle and protocell formation. However, the mechanism by which amphiphilic molecules are formed from small prebiotically plausible molecules, which spontaneously self-assemble to protocells, remains to be elucidated. ^6,7 Furthermore, a process for the selective formation of membrane molecules of defined length, such as those found in most cellular structures, remains elusive. Here we demonstrate that a reaction cascade starting from prebiotically accessible acetaldehyde under organocatalysis with prebiotic imidazolidine-4-thione rapidly yields lipid molecules that form protocells by a spontaneous self-assembly. In this process, lipids with up to C20 in length develop a membrane, which additionally incorporates the organocatalyst at the liquid-lipid interface in a self-evolutionary modification. The chemical formation and assembly were monitored by dynamic light scattering, fluorescence microscopy, (cryo)-TEM and in-situ high-resolution mass spectrometry. The size of these catalytically active vesicles and protocells ranges from ~11 nm up to 7 μm. These results demonstrate that an organocatalyst formed from prebiotic molecules such as H ₂ S, NH ₃ , H ₂ O, HCN and aldehydes catalyses the selective formation of lipids, facilitating spontaneous compartmentalisation. This finding unveils a novel pathway that enables protocell formation without the necessity of amphiphilic compounds being present from the start. Furthermore, we found that these protocells concentrate organic molecules and create a water-poor, lipophilic reaction environment that facilitates transformations that are difficult to achieve in water.