EPFL Scientists Decode Nanopore Mysteries, Paving Way for Advanced Biosensors and Brain-like Computers
- MM24 News Desk
- 4 hours ago
- 3 min read
Researchers at EPFL have solved the long-standing mystery of why biological nanopores behave unpredictably, discovering that electrical charges control both rectification and gating effects. The team led by Professors Matteo Dal Peraro and Aleksandra Radenovic used engineered pore variants to demonstrate how charge distribution creates one-way ion valves and temporary pore collapse, enabling them to design nanopores that mimic synaptic plasticity for future bio-computing systems.
For years, scientists working with biological nanopores have faced a puzzling phenomenon: these incredibly useful molecular gates would sometimes suddenly stop working for no apparent reason. Like a light switch that flickers off unexpectedly, the flow of ions through these tiny pores would abruptly cease, disrupting sensitive applications from DNA sequencing to disease detection.
Now, researchers at the Ecole Polytechnique Fédérale de Lausanne (EPFL) have not only discovered why this happens but have learned to control it—opening doors to revolutionary biosensors and computers that process information using ions instead of electrons.
The research team, co-led by Professor Matteo Dal Peraro and Professor Aleksandra Radenovic at EPFL, tackled two particularly frustrating nanopore behaviors that have baffled scientists for decades. The first, called "rectification," occurs when ions flow more easily in one direction than the other, like a molecular check valve.
The second, "gating," involves the sudden, temporary shutdown of ion flow entirely. Both phenomena have significantly limited the reliability of nanopore technology despite its tremendous potential.
"Understanding these effects required looking at nanopores not just as passive holes but as dynamic electrical systems," explained Professor Dal Peraro. The team focused their investigation on aerolysin, a bacterial pore protein commonly used in sensing applications.
In a brilliant experimental design, they systematically created 26 different mutant versions of the nanopore, each with specific charged amino acids altered along its inner surface. This meticulous approach allowed them to map exactly how electrical charges influence nanopore behavior.
What they discovered was a sophisticated molecular dance governed by electrical forces. The researchers found that rectification occurs because the pattern of positive and negative charges lining the pore's interior creates an inherent directionality to ion flow. "It's like having a one-way street for ions," said Professor Radenovic. "The charge distribution makes it naturally easier for ions to move in one direction than the other, creating the rectification effect that scientists have observed for years."
The more dramatic gating phenomenon turned out to have a different mechanism altogether. When too many ions rush through the pore too quickly, they create a charge imbalance that physically destabilizes the nanopore's structure.
This causes part of the protein to temporarily collapse, blocking further ion passage until equilibrium is restored. The team confirmed this by engineering more rigid nanopore structures that completely eliminated gating, proving that pore flexibility is essential to the process.
The implications of this understanding are profound. Scientists can now design nanopores with specific charge patterns to control exactly when and how they gate. For sensing applications like DNA sequencing, engineers can create pores that minimize gating to ensure uninterrupted reading of genetic material. But perhaps even more exciting is the potential for bio-inspired computing.
The EPFL team demonstrated this by building a nanopore system that mimics synaptic plasticity—the fundamental mechanism by which neural connections in the brain strengthen or weaken through experience. Their engineered nanopore could "learn" from electrical voltage pulses, changing its gating behavior in response to different patterns of stimulation, much like a biological synapse adapts to neural activity.
"This represents a significant step toward ion-based processors that could one day complement or even replace conventional electronics," noted Professor Dal Peraro. Such systems would process information using the same ionic language that biological systems use, potentially enabling more efficient computation and direct interfaces with living tissues.
The research, which combined sophisticated experiments with advanced simulations and theoretical modeling, provides a comprehensive physical framework for understanding and engineering biological nanopores. By uncovering the fundamental principles governing these molecular gates, the EPFL team has transformed nanopores from unpredictable tools into programmable components for next-generation biotechnology and computing.
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