Design of artificial biomimetic channels with Na⁺ permeation rate and selectivity potentially outperforming the natural sodium channel

Artificial ion channels that enable high-efficiency ion transport have important implications in nanofluidics and biomedical applications such as drug delivery. Herein, we show a simulation-based chemical design of a biomimetic sodium channel that possesses permeation rate and selectivity potentially higher than those of the state-of-the-art natural vertebrate voltage-gated sodium channels. Importantly, our theoretical findings have undergone empirical testing, aligning well with the Arrhenius law as derived from a diverse range of experimental results. The high-efficiency ion transport is achieved by anchoring the carboxylate functional groups within the channel filter. A key chemical guiding principle underlying the ion channel design is that the free-energy barrier for the Na⁺ passage across the channel should be comparable to typical thermal energy at room temperature. With the implementation of the chemical design, we found that the relatively low free-energy barrier can be attributed to the compensation effect of the carboxylate groups to the partially lost oxygen shell of the ion within the ion channel, as well as to the consonant vibration of the ions inside and outside the channel. This mechanistic understanding brings new insight, at the molecular level, into the high-efficiency ion transport across the designed membrane channels. The proof of principle achieved from the simulations will stimulate future experimental confirmation and potential applications of the high-performance artificial channels in nanofluidics and in bioinspired iontronics.