Scientists create a 'mirror molecule' that attacks tumors without harming healthy cells

Scientists built the first fully functional mirror-image pore; and, in lab assays, it lowered survival of aggressive breast cancer cells by about 27 percent.

The work spans India and Germany, with experiments led at the Rajiv Gandhi Center for Biotechnology (RGCB) and simulations from Constructor University in Bremen.

What is a mirror-image pore?

Proteins in living cells are made from L-amino acids, while D-amino acids, mirror versions of natural amino acids, flip the usual molecular handedness and often resist enzymes.

The team assembled a membrane pore from D-peptides called DpPorA, then created a charge-tuned variant that steered ions and molecules more precisely.

Their paper details how altering a few residues boosted conductance and sharpened selectivity without losing stability.

Researchers noted that this class of mirror-image pores could help advance the development of molecular sensors and therapeutics. 

Testing the mirror pore claim

To confirm the pore truly mirrors its natural twin, the scientists paired electrical recordings with molecular dynamics, computer simulations that track atoms under physical forces.

The D-pore and its L-pore analog carried similar ion currents, which is expected because permeating ions are achiral, and their radius profiles over time matched closely.

In simulations under an applied voltage, conductance values remained high and stable while atom-level maps showed a positively charged lumen that attracts anions.

That charge layout explained why the charge-edited version bound certain peptides longer before releasing them.

Membranes themselves are chiral, and that property can bias what crosses them. A study found lipid bilayers can be enantioselectively permeable, favoring one handed form of a molecule over the other.

That broader context helps explain why a D-peptide pore can behave differently in cells than an L-peptide pore, even when their shapes appear like perfect reflections.

Sensing and moving

The mirror-image pores sensed single peptides, PEG-decorated polypeptides, cyclic sugars, and full-length alpha-synuclein, a nerve protein linked to Parkinson’s disease symptoms.

In each case, transient current blockades revealed how long the analyte lingered inside the pore.

Other studies have shown that nanopores can detect clumps of the alpha-synuclein protein directly from patient samples, proving how useful this method is for spotting disease-related proteins.

In giant unilamellar vesicles, the D-pores formed large, flexible channels and ferried dyes of increasing size in a time-dependent way. Control vesicles stayed dark even after 45 minutes, which signaled the pore itself enabled transport.

The group also compared cis and trans side interactions, finding asymmetry that mapped to where positive charge was concentrated. That asymmetry supported the design logic behind the charge-tuned variant.

Early signs of cancer selectivity

In cultured triple-negative breast cancer cells, the charge-tuned D-pore reduced cell viability by about 11 percent at 10 micromolar, 19 percent at 20 micromolar, and 27.21 percent at 25 micromolar.

Normal mammary cells showed no significant effect at 20 micromolar, suggesting the pore’s surface charge targets the more negatively charged tumor membranes.

Imaging with a fluorescent tag showed the peptide accumulating in membranes over 4 hours and increasing by 24 hours.

These findings align with how many anticancer peptides work. They attach to and break down tumor cell membranes instead of targeting a single enzyme, and their small size allows them to move easily through tissue, carry drugs, or directly trigger cancer cell death.

Because the pore is built from D-amino acids, it resisted common proteases that would normally chop peptide drugs quickly. That biochemical staying power could support lower dosing and longer action in future tests.

Mirror pores and future healthcare

Nanopores were first developed for reading DNA and RNA, but today they are also used to detect proteins, sugars, and other complex molecules.

Researchers have found that these technologies show strong potential for medical sensing, similar to what the new mirror-image pores are already showing.

DpPORA’s high conductance and flexible geometry are useful for reading diverse molecular signatures. Its charge-tuned sibling adds control over what binds and how fast it passes, which is the kind of dial a practical sensor or therapy needs.

Selectivity in cells is encouraging, but translation demands careful toxicology, dose finding, and immune profiling in animals. It also requires scalable synthesis, lot-to-lot consistency, and device integration for sensing.

One near-term path is a hybrid strategy, pairing a mirror-image pore with a targeted payload that only activates inside tumor tissues.

Another is a label-free diagnostic chip that flags disease proteins at the single-molecule level from small blood or cerebrospinal fluid samples.

The study is published in Nature Communications.

—–

Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates. 

Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com.

—–