A team from EPFL has revealed that biological nanopores engineered by researchers exhibit electrical signal responses that resemble learning-like behavior.
The nanopores alter their behavior after receiving multiple electrical pulses, rather than functioning as simple ion channels, according to the team’s study, published in Nature Nanotechnology. The findings demonstrate that engineered nanopores can retain past signals, suggesting they could serve as fundamental components in the development of ion-based computer systems.
The discovery broadens the capabilities of engineered nanopores, in that, along with their current uses in DNA sequencing and molecular sensing, these structures could help build protein-based computers in the future. Nanopores might also lead to new forms of biotechnology by processing information through the flow of ions.
A Long-Standing Mystery in a Tiny Channel
Nanopores allow charged particles to move across cell membranes. Most of the electrical patterns they create are predictable, but some nanopores exhibit unexpected behavior. Some suddenly slow in current, change timing, or even reverse the direction of ion flow when voltage shifts occur.
Scientists have struggled to understand a pair of related phenomena that have remained unexplained for many years. The first of these, known as rectification, is where ions move more easily in one direction than the other. Gating, on the other hand, is where the current abruptly slows or stops, as if the pore temporarily collapses.
These unpredictable behaviors make it difficult to use nanopores for tasks such as DNA sequencing, which requires a steady current. The EPFL researchers Matteo Dal Peraro and Aleksandra Radenovic, together with their team, studied whether the observed problems stemmed from chemical alterations inside the pore or from undetected structural changes.
Rewiring A Protein Channel
The researchers used aerolysin, a pore-forming bacterial protein, for the experiment due to its compact structure and well-documented composition, which makes it suitable for laboratory modifications. The team modified the arrangement of charged amino acids inside the channel to create 26 different versions of aerolysin. Each modified pore had a distinct electrical layout that affected how ions moved through it.
Alternating-voltage sweeps were then applied to distinguish between electrical and mechanical effects in their system. The team observed that rectification began immediately when the voltage switched direction, but gating behavior did not appear until multiple cycles and took multiple seconds to develop. The researchers used this timing difference to study each behavior independently.
Charge vs Motion
The team discovered that rectification arises from an unequal charge distribution within the pore structure. The direction of ion flow depends on the number of charged amino acids located on each side of the pore. The placement and type of amino acids used allow scientists to control, enhance, or even reverse this effect.
The gating process operates through a separate mechanism. The movement of ions through the pore creates an imbalance of charges, leading to protein deformation and a temporary blockage of current. The protein structure behaves like a hinge, rapidly opening and closing in response to changes in internal stress.
Two lab tests confirmed these results. When the internal charge changed, the gating direction also reversed. When the protein stiffened, gating stopped altogether. This shows that both the protein’s flexibility and the arrangement of its charges are essential to this process.
A Protein That Adapts to Its Electrical Past
The researchers studied pores that demonstrated strong responses to repeated electrical pulses. The pore conductance measurements showed a direct relationship with applied voltage and also displayed changes based on prior electrical exposure.
The channel’s response pattern became more defined with each successive pulse application. The channel began to reflect its electrical history in its performance. The pore itself was not actually thinking; however, its structure and charge arrangement enabled a basic form of learning.
Ion-Based Computing
Engineers can create pores with specific functions by implementing the principles of rectification and gating. The charge distribution in DNA sequencing and sensing systems can also be modified to minimize unwanted gating effects. Additionally, these behaviors could be harnessed for useful features in ion-based computing.
The protein’s built-in properties produce learning-like effects that ion-based processors can utilize without requiring additional circuitry. An engineered pore can function as both a sensor and a memory device while consuming very little energy.
The research demonstrates that nanopores can be engineered to detect changes, learn, and remember information, making them suitable for biomimetic applications.
Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds a Master of Business Administration and a Bachelor of Science in Business Administration, as well as a certification in Data Analytics. His work combines analytical training with a focus on emerging science, aerospace, and astronomical research.