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Scientists found that nanopores’ electrical charges control how ions flow and when pores temporarily shut down. The discovery could allow engineers to design nanopores that “learn” like synapses for next-generation computing.
Pore-forming proteins appear across many forms of life. In humans, they help protect the body by supporting immune defenses. In bacteria, they often function as toxins that create openings in cell membranes. These natural pores regulate the movement of ions and molecules, and their precise control over molecular transport has made them valuable in biotechnology, including DNA sequencing and molecular sensing.
Unpredictable Behavior in Ion Flow
Even with their importance in research and technology, biological nanopores can behave in ways that are difficult to predict. Scientists still lack a complete explanation for how ions travel through these pores or why ion movement can suddenly stop.
A pair of long-standing mysteries has been especially challenging to explain: rectification and gating. Rectification describes a change in ion flow depending on the “sign” (plus or minus—positive or negative) of the applied voltage. Gating occurs when ion flow suddenly drops. These effects, particularly gating, can disrupt sensing applications and have remained only partially understood.
Identifying the Forces Behind Rectification and Gating
A research team led by Matteo Dal Peraro and Aleksandra Radenovic at EPFL has now clarified the physical origins of these behaviors. Through a combination of experiments, computational modeling, and theoretical work, they revealed that both rectification and gating arise from the electrical charges within the nanopore and how these charges interact with moving ions.
Testing Charge Patterns in Engineered Nanopores
The group investigated aerolysin, a bacterial pore frequently used in sensing studies. By altering the charged amino acids that line the pore’s interior, they created 26 versions of the nanopore, each with a different arrangement of charges. The researchers then measured how ions moved through each modified pore under various experimental conditions.
To explore how rectification and gating appear over time, the team applied alternating voltage signals. This approach helped them distinguish fast rectification processes from slower gating behavior. They then used biophysical models to interpret the results and identify the underlying mechanisms.
Insights Into Ion Flow and Structural Stability
The study showed that rectification occurs because the pore’s internal charge distribution affects how easily ions can move, allowing them to travel more readily in one direction than the other. Gating results from a different process: when a strong flow of ions creates a charge imbalance, the pore becomes structurally unstable. A portion of the pore temporarily collapses, blocking ion movement until the structure reopens.
Both behaviors depend on the amount and precise location of charge inside the nanopore, as well as whether those charges are positive or negative. By adjusting the charge “sign,” the researchers were able to influence when gating occurred and under what conditions. They also discovered that making the pore more rigid eliminates gating entirely, showing that structural flexibility is essential for this effect.
Toward Programmable and Adaptive Nanopores
These findings provide a roadmap for designing biological nanopores tailored for specific uses. Engineers can now modify pores to resist gating in sensing technologies or intentionally incorporate gating for applications in bio-inspired computing. In one demonstration, the team created a nanopore that mimics synaptic plasticity, “learning” from voltage pulses in a way that resembles a neural synapse. This type of adaptive behavior suggests that future ion-based processors could one day use nanopores as core components.
Reference: “Lumen charge governs gated ion transport in β-barrel nanopores” by Simon Finn Mayer, Marianna Fanouria Mitsioni, Paul Robin, Lukas van den Heuvel, Nathan Ronceray, Maria Jose Marcaida, Luciano A. Abriata, Lucien F. Krapp, Jana S. Anton, Sarah Soussou, Justin Jeanneret-Grosjean, Alessandro Fulciniti, Alexia Möller, Sarah Vacle, Lely Feletti, Henry Brinkerhoff, Andrew H. Laszlo, Jens H. Gundlach, Theo Emmerich, Matteo Dal Peraro and Aleksandra Radenovic, 11 November 2025, Nature Nanotechnology.
DOI: 10.1038/s41565-025-02052-6
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