Biology is a very deep source of inspiration for technological progress. Having motivated the birth of artificial neural networks, it is currently serving as a source of additional inspiration for a different paradigm in computer architectures, neuromorphic computing.

Signal transmission in the brain relies on voltage-gated ion channels, complex machines with moving parts and complex interactions. These types of ion channels are difficult to design from the ground up, but their behaviour seems essential for the low power functioning of the brain.

From an electronic point of view, it can be said that the brain is working in an iontronic regime, with ions serving the purpose of charge carriers. Not only that, but ion channels seem to exhibit the electrical behaviour of memristors, resistors with memory.

We set out to find a simpler mechanism for voltage gating, one that didn't depend on an allosteric mechanism and an intricate network of moving parts, and one which could be tuned and engineered. We found hydrophobic gating to be a strong candidate for this mechanism.

Nanobubbles and voltage

Having studied the formation of nanobubbles in small hydrophobic nanopores, which effectively blocked the conductivity across them, so-called hydrophobic gating, we were interested in the reported effect that had on opening such gates.

We developed a theory which, backed by molecular dynamics simulations, could predict the effect of voltage on the wetting dynamics of hydrophobic nanopores. Using that framework, we found that due to the deep metastability between dry (non-conductive) and wet (conductive) states, hydrophobic nanopores would have a hysteretic behaviour when an alternating voltage is supplied. This behaviour is the hallmark of memristors.

Bio-inspiration strikes back

Guided by these simulations, we map the interest region where pure hydrophobic gating could take place. Biological nanopores are proved themselves to be the ideal candidate. These are short, 3 to 10 nm long, narrow, with diameters that can be down to 1 nm, are highly tunable, because targeted mutations can alter the pore's conductive regime.

We focused on Fragaceatoxin C  (FraC), a pore used in single-molecule nanopore sensing and which has been extensively mutated to improve its performance on different task, like the capture of molecules.  We used our molecular dynamics protocol in a mutated FraC pore, one which had two additional hydrophobic residues, and found that if one considered a low pH environment the state where a nanobubble was present was the most probable, while for neutral pH this state did not exist. 

Electrophysiological experiments also confirmed this, with single pore recording showing spontaneous switching between conductive and non-conductive states. This lead us to perform alternating current experiments, which indeed showed the expected memristive behaviour. 

Iontronic memristive device 

By having multiple FraC channels in a single membrane, it is possible to prototype a device that works similarly to a synapse, and have short term plasticity. When under positive voltage signals, the device becomes sequentially more conductive (learning) and while under negative voltage signals, the device becomes sequentially less conducive (forgetting).

Although still in its early stages, we believe that hydrophobic gating could serve as a platform for iontronic switches and memristive devices for future iontronic applications, and are actively searching for new systems, also in the solid state realm, that could be used for these applications.

A hydrophobically gated memristive nanopore  (HyMN)-based device has  important strengths: they are energy efficient, nanometer-sized, have no moving parts, are highly reproducible and economical, and advanced technologies are available to fine tune their properties