Mirror-image nanopores may advance biomedical research

For the first time, a team of researchers from Constructor University, the Rajiv Gandhi Centre for Biotechnology in India, and additional partner institutions has succeeded in fabricating and characterizing a mirror-image nanopore built entirely from D-amino acids. This achievement, published in Nature Communications, represents a significant step toward new biomedical applications, including potential cancer treatments.

“Our simulations provided the molecular-level picture needed to prove that these mirror-image pores are exact counterparts of their natural analogues,” says Prof. Ulrich Kleinekathöfer, Professor of Physics at Constructor University in Bremen and co-author of the study.

In nature, proteins are almost exclusively composed of L-amino acids, while D-amino acids occur only rarely. Constructing complete proteins from D-amino acids is a complex process, but it offers substantial advantages: such mirror-image structures are more resistant to degradation and interact differently with biological systems.

The research team designed a synthetic D-peptide pore, named DpPorA, that forms stable molecular channels. By adjusting the charge distribution, they developed modified versions of these pores with enhanced conductance and selectivity under varying salt conditions.

Experimental data showed that the DpPorA pores can detect a broad range of biomolecules, including peptides, cyclic sugars, and specific proteins relevant to Parkinson’s disease research. Fluorescence microscopy confirmed that the pores form large and flexible membrane channels, capable of size-dependent molecular transport.

“The computational work gave us the confidence that we were indeed looking at a true mirror-image pore,” explains Dr. Kalyanashis Jana, postdoctoral researcher in Kleinekathöfer’s group and equally contributing first author.

Simulations conducted by Constructor University scientists confirmed that the artificial D-pore is a precise structural reflection of its natural L-form, while revealing subtle differences in molecular behavior. The research also demonstrated selective cytotoxicity in cell studies: fluorescently labeled mirror-image pores disrupted cancer cell membranes but left healthy cells unaffected.

This selectivity points to possible applications in targeted cancer therapy and marks a promising step for nanopore-based medical technologies.

MEDICA-tradefair.com; Source: Constructor University