The self-assembly of prebiotically plausible amphiphiles (fatty acids) to form a bilayer membrane for compartmentalization is an important factor during protocellular evolution. Such fatty acid-based membranes assemble at relatively high concentrations, and they lack robust stability. We have demonstrated that a mixture of lipidated lysine (cationic) and prebiotic fatty acids (decanoic acid, anionic) can form protocellular membranes (amino acid-based membranes) at low concentrations via electrostatic, hydrogen bonding, and hydrophobic interactions. The formation of vesicular membranes was characterized by dynamic light scattering (DLS), pyrene and Nile Red partitioning, cryo-transmission electron microscopy (TEM) images, and glucose encapsulation studies. The lipidated nonproteinogenic analogues of lysine (Lys), such as ornithine (Orn) and 2,4-diaminobutyric acid (Dab), also form membranes with decanoate (DA). Time-dependent turbidimetric and 1H NMR studies suggested that the Lys-based membrane is more stable than the membranes prepared from nonproteinogenic lower analogues. The Lys-based membrane embeds a model acylating agent (aminoacyl-tRNA mimic) and facilitates the colocalization of substrates to support regioselective peptide formation via the α-amine of Lys. These membranes thereby assist peptide formation and control the positioning of the reactants (model acylating agent and −NH2 of amino acids) to initiate biologically relevant reactions during early evolution.

The proteinogenic lysine (Lys) and arginine (Arg) have multiple methylene groups between α-carbon and terminal charged centre. Why nature did not select ornithine (Orn), 2,4-diamino butyric acid (Dab) and 2,3-diamino...

Templated assembly of small molecules into nano-structural architectures has been used extensively by nature throughout its evolution. These systems were also studied in artificial systems to design phosphate templated assembly....

Prebiotic membranes are one of the essential elements of the origin of life because they build compartments to keep genetic materials and metabolic machinery safe. Since modern cell membranes are made up of ethanolamine-based phospholipids, prebiotic membrane formation with ethanolamine-based amphiphiles and phosphates might act as a bridge between the prebiotic and contemporary eras. Here, we report the prebiotic synthesis of O-lauroyl ethanolamine (OLEA), O-lauroyl methyl ethanolamine (OLMEA), and O-lauroyl dimethylethanolamine (OLDMEA) under wet–dry cycles. Turbidimetric, NMR, DLS, fluorescence, microscopy, and glucose encapsulation studies highlighted that OLEA-ATP and OLMEA-ATP form protocellular membranes in a 3:1 ratio, where ATP acts as a template. OLDMEA with a dimethyl group did not form any membrane in the presence of ATP. ADP can also template OLEA to form vesicles in a 2:1 ratio, but the ADP-templated vesicles were smaller. This suggests the critical role of the phosphate backbone in controlling the curvature of supramolecular assembly. The mechanisms of hierarchical assembly and transient dissipative assembly are discussed based on templated-complex formation via electrostatic, hydrophobic, and H-bonding interactions. Our results suggest that N-methylethanolamine-based amphiphiles could be used to form prebiotic vesicles, but the superior H-bonding ability of the ethanolamine moiety likely provides an evolutionary advantage for stable protocell formation during the fluctuating environments of early earth.

Access to the interior of the cell by destabilizing the natural barrier of the cell membrane is fundamental to drug and therapeutic delivery. Taking the unique facial amphiphilicity advantage of cholic acid to facilitate switching over impermeable cellular membranes, we report the synthesis of three different series of charge variable (anionic, cationic, and neutral) amphiphilic copolymers with various cholate contents and their membrane destabilization behavior. The synthesized cholate-containing amphiphilic copolymers self-organized into 80−100 nm sized nanoaggregates in aqueous media, while cholate moieties resided in the core of the self-assembled nanoparticles, as confirmed by 1 H NMR spectroscopy. The cholate-containing polymeric micelles proficiently destabilized the liposomes at pH 5.0 and pH 7.4. Interestingly, the cholate-appended neutral polymer exhibited up to 15fold enhancement in the membrane destabilization efficiency in comparison with respective cholate-based anionic or cationic polymers. Mechanistic studies using fluorescence, dynamic light scattering, and transmission electron microscopy established that the polymer−membrane interaction, subsequent reorganization, and insertion of cholate into the bilayer play a crucial role. Model drug (Nile red) encapsulation and release studies suggested the therapeutic potential of the cholate-conjugated polymeric nanoclusters.