This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: In a promising milestone for nanotechnology, Constructor University has contributed to a study demonstrating self-assembling nanopores capable of detecting disease proteins associated with illnesses like Parkinson's and ALS. The international research project, published in Nature Nanotechnology, produced synthetic nanoscale pores that adjust like a camera aperture to capture and analyze different proteins at low concentrations—even distinguishing between healthy proteins and the dangerous mutated versions that contribute to disease.
Constructor University professor Dr. Ulrich Kleinekathöfer and postdoctoral researcher Dr. Kalyanashis Jana contributed computational expertise to the study led by Dr.
Kozhinjampara Mahendran at the Rajiv Gandhi Center for Biotechnology in India. "We supported the experimental work done by our colleagues in India by providing computational simulations that allow us to learn the molecular-level details of these nanopores and their sensing of analytes," Kleinekathöfer said. "Our simulations helped with the rational design of flexible, synthetic pores that can intrinsically detect disordered proteins.
We know these molecules contribute to neurodegenerative diseases like Parkinson's, but they are notoriously difficult to study using conventional methods because they constantly change shape," Kleinekathöfer explained. The innovation lies in the nanopores' flexibility. By strategically incorporating a single unnatural amino acid into a designed peptide, the research team effectively created molecular sensors that can adjust between small and large diameters while maintaining their structural foundation.
This versatility allows the same basic design to detect different types of disease proteins. The larger pores excel at capturing and analyzing α-synuclein, a protein whose abnormal clumping is a primary hallmark of Parkinson's disease. The nanopores achieved nanomolar sensitivity, meaning they were able to detect trace amounts of the protein, and could also distinguish between different disease-causing mutations even within heterogeneous mixtures.
Smaller pores also successfully detected peptides associated with ALS and cellular death. Conventional techniques like enzyme-linked immunosorbent assays (ELISA) or mass spectrometry require larger sample volumes, often cannot detect proteins at such low concentrations and typically cannot distinguish between different aggregation states in real time. By contrast, the nanopore approach provided single-molecule resolution with minimal sample requirements.
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