Fatty Acid/Phospholipid Blended Membranes: A Potential Intermediate State in Protocellular Evolution

Abstract

Prior to the evolution of membrane proteins, intrinsic membrane stability and permeability to polar solutes are essential features of a primitive cell membrane. These features are difficult to achieve simultaneously in model protocells made of either pure fatty acid or phospholipid membranes, raising the intriguing question of how the transition from fatty acid to phospholipid membranes might have occurred while continuously supporting encapsulated reactions required for genomic replication. Here, the properties of a blended membrane system composed of both oleic acid (OA), a monoacyl fatty acid, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), a diacyl phospholipid are described. This hybrid vesicle system exhibits high stability to divalent cations (Mg ), while simultaneously maintaining its permeability to small charged molecules such as nucleotides and divalent ions such as Mg . This combination of features facilitates key reactions expected to occur during a transition from primitive to modern cells, including nonenzymatic RNA replication, and is also compatible with highly evolved functions such as the ribosomal translation of a protein. The observations support the hypothesis that the early transition from fatty acid to phospholipid membranes could be accomplished through intermediate states in which membranes are composed of amphiphile mixtures, and do not require protein transporters.

Membrane Tension–Mediated Growth of Liposomes

“…Furthermore, we can rule out that fatty acids themselves mediate or trigger growth without the need of membrane tension, as previous studies have clearly shown that hybrid vesicles are able to grow only in presence of pure fatty acid vesicles, and not in presence of hybrid vesicles . This observation is further strengthened by a recent study, where the surface area of hybrid vesicles with 50% or higher phospholipid content was shown to remain completely constant in presence of Mg 2+ , proving the ability of phospholipids to efficiently retain the fatty acids in the hybrid membranes …”

“…Alternatively, fatty acid vesicles are studied as a model system for protocells that are hypothesized to have been involved in the emergence of life on the early earth. Bridging the gap between the protocells and the modern cells, hybrid vesicles, which are composed of both lipids and fatty acids, have been studied as yet another model system . These hybrid systems are also potentially interesting scaffolds for synthetic cells as they exhibit a valuable combination of features, in particular an enhanced stability against Mg 2+ , while retaining permeability to small charged molecules .…”

Microfluidics for Biosynthesizing: from Droplets and Vesicles to Artificial Cells

“…Fabrication of environments compatible artificial lipid bilayers which possess a robust structure are highly significant for artificial cells development. [201] Castell and co-workers reported the fabrication of lipid bilayers in the hydrogel shell by microfluidics ( Figure 8B). [202] In this work, the structure of artificial cells can be adjusted by controlling the number of internal droplets and compositions.…”

Cell Fuelling and Metabolic Energy Conservation in Synthetic Cells

“…Vesicle structures can form spontaneously from fatty acids, as first reportedi n1 973, [44] and such membranes mightay have surrounded the first cells. [47] Well-sealed, stable membranes can also be formed from block copolymers, [48] but the functional incorporation of integral membranep roteins is challenging, especially when the proteins requirespecific lipids as cofactors. Fatty acid-phospholipid blended membranes display increased stabilityb ut still maintain permeability for small (charged) solutes.…”

“…They might have formed an intermediate in protocellulare volution, which allowed membrane passage withouttransporters. [47] Well-sealed, stable membranes can also be formed from block copolymers, [48] but the functional incorporation of integral membranep roteins is challenging, especially when the proteins requirespecific lipids as cofactors. The majority of successfulr econstitutions in non-native amphiphilic membranes involver elativelys table membrane pores or channels that do not undergo large conformational changes in the membrane.…”