Bioinspired Artificial Sodium and Potassium Ion Channels

Abstract

In Nature, all biological systems present a high level of compartmentalization in order to carry out a wide variety of functions in a very specific way. Hence, they need ways to be connected with the environment for communication, homeostasis equilibrium, nutrition, waste elimination, etc. The biological membranes carry out these functions; they consist of physical insulating barriers constituted mainly by phospholipids. These amphipathic molecules spontaneously aggregate in water to form bilayers in which the polar groups are exposed to the aqueous media while the non-polar chains self-organize by aggregating to each other to stay away from the aqueous media. The insulating properties of membranes are due to the formation of a hydrophobic bilayer covered at both sides by the hydrophilic phosphate groups. Thus, lipophilic molecules can permeate the membrane freely, while the small charged or very hydrophilic molecules require the assistance of other membrane components in order to overcome the energetic cost implied in crossing the non-polar region of the bilayer. Most of the large polar species (such as oligosaccharides, polypeptides or nucleic acids) cross into and out of the cell via endocytosis and exocytosis, respectively. Nature has created a series of systems (carriers and pores) in order to control the balance of small hydrophilic molecules and ions. The most important structures to achieve these goals are the ionophoric proteins that include the channel proteins, such as the sodium and potassium channels, and ionic transporters, including the sodium/potassium pumps or calcium/sodium exchangers among others. Inspired by these, scientists have created non-natural synthetic transporting structures to mimic the natural systems. The progress in the last years has been remarkable regarding the efficient transport of Na(+) and K(+) ions, despite the fact that the selectivity and the ON/OFF state of the non-natural systems remain a present and future challenge.

Self-assembling Venturi-like peptide nanotubes

“…5 These membrane nanotubes mimic the structure and properties of natural ion channels. 6 Although the SCPNs compete with them in the transport efficiency of alkali ions, the ion selectivity is far from the natural systems. In addition, studies carried out with transmembrane SCPNs have shown that some transport selectivity can be achieved playing with nanotube internal diameter, 5 e.g., decapeptides efficiently transported glucose or glutamic acid while octapeptides did not.…”

“…7 The remarkable combination of efficiency and transport selectivity of natural ions channel continues spurring the scientific interest in the design of improved artificial systems. 6 Some of the protein channels, such as potassium channels, 8 have a shape characterized by the presence of a selectivity filter in the centre of the channel that is preceded by a dilated water-filled chamber. Therefore the form of the internal cavity of these proteins resembles the shape of Venturi tubes.…”

Ion–Ion Selectivity of Synthetic Membranes with Confined Nanostructures

“…One-dimensional hollow spaces are found in well-aligned and uniform nanochannels, 35 nanotubes, 36 synthetically designed channels, 37,38 and crystalline building blocks with ordered channels. 39,40 These spaces act as linear channels, confining the configuration and pathway of ions along the axial direction when ions enter the channel.…”

Low Molecular Weight Di‐ to Tetrapeptide Transmembrane Cation Transporters

“…Selective transport of cations across the cell membrane is important for many fundamental biological processes such as maintaining the resting potential of cells, skeletal muscle contraction, nerve impulse transmission and hormonal secretion. [ 1–5 ] Natural ion transporters have complex structures and are typically made of large proteins. [ 1,2 ] Despite the high ion‐selectivity and precise functions of natural ion transporters, their poor in vitro stability has inspired researchers to develop stable and structurally simple biomimetic ion transporters.…”