Semipermeable Mixed Phospholipid-Fatty Acid Membranes Exhibit K+/Na+ Selectivity in the Absence of Proteins

Abstract

Two important ions, K+ and Na+, are unequally distributed across the contemporary phospholipid-based cell membrane because modern cells evolved a series of sophisticated protein channels and pumps to maintain ion gradients. The earliest life-like entities or protocells did not possess either ion-tight membranes or ion pumps, which would result in the equilibration of the intra-protocellular K+/Na+ ratio with that in the external environment. Here, we show that the most primitive protocell membranes composed of fatty acids, that were initially leaky, would eventually become less ion permeable as their membranes evolved towards having increasing phospholipid contents. Furthermore, these mixed fatty acid-phospholipid membranes selectively retain K+ but allow the passage of Na+ out of the cell. The K+/Na+ selectivity of these mixed fatty acid-phospholipid semipermeable membranes suggests that protocells at intermediate stages of evolution could have acquired electrochemical K+/Na+ ion gradients in the absence of any macromolecular transport machinery or pumps, thus potentially facilitating rudimentary protometabolism.

Artificial Cells: Past, Present and Future

“…183 Zhou et al recently found that vesicles with membranes containing both fatty acids and phospholipids selectively retain potassium and exclude sodium, and a transmembrane gradient can be established for these ions without a protein pump. 184 The authors showed that simply adjusting the lipid content of vesicle membrane adjusts the ion permeability of the artificial cell membrane. However, the best strategy to regulate the permeability of an artificial cell membrane is to imitate natural cells and construct an ATPdependent membrane-associated protein pump to maintain ion gradients and concentrate metabolites.…”

“…Therefore, a vesicle membrane containing both fatty acids and phospholipids is suitable for some applications that require increased permeability . Zhou et al recently found that vesicles with membranes containing both fatty acids and phospholipids selectively retain potassium and exclude sodium, and a transmembrane gradient can be established for these ions without a protein pump . The authors showed that simply adjusting the lipid content of vesicle membrane adjusts the ion permeability of the artificial cell membrane.…”

Protocells: Milestones and Recent Advances

“…The K + /Na + selectivity of the mixed fatty acid‐phospholipid semipermeable membranes suggests that protocells could have established electrochemical K + /Na + ion gradients in the absence of macromolecular transport machinery or pumps, thus potentially facilitating a rudimentary metabolism. [ 175 ] In a study where four fatty acid mixtures were subjected to laboratory buffers and liquid samples obtained from hot springs, only mixtures of fatty acid and its glycerol derivatives were found to form vesicles in natural water. [ 176 ] The authors advise caution that the transition from the laboratory to a more realistic natural environment can lead to dramatic changes in behavior.…”

Membrane Mimetic Chemistry in Artificial Cells

“…Vesicle membranes that contain both fatty acid and phospholipid may therefore be appropriate platforms for some applications that require increased permeability. Demonstrating this concept, Zhou et al recently examined ion permeability in hybrid phospholipid/fatty acid vesicles . Interestingly, they found that hybrid vesicles selectively retained potassium and excluded sodium, establishing transmembrane gradients for these ions in the absence of any protein-based pumps.…”

“…Demonstrating this concept, Zhou et al recently examined ion permeability in hybrid phospholipid/fatty acid vesicles. 63 Interestingly, they found that hybrid vesicles selectively retained potassium and excluded sodium, establishing transmembrane gradients for these ions in the absence of any protein-based pumps. This suggests that membrane permeability to ions in artificial cells can be modulated by simply adjusting membrane lipid content.…”