Results
Title

PlyAB Nanopores Detect Single Amino Acid Differences in Folded Haemoglobin from Blood**.

Authors

Huang, Gang; Voorspoels, Aderik; Versloot, Roderick Corstiaan Abraham; van der Heide, Nieck Jordy; Carlon, Enrico; Willems, Kherim; Maglia, Giovanni

Abstract

The real‐time identification of protein biomarkers is crucial for the development of point‐of‐care and portable devices. Here, we use a PlyAB biological nanopore to detect haemoglobin (Hb) variants. Adult haemoglobin (HbA) and sickle cell anaemia haemoglobin (HbS), which differ by just one amino acid, were distinguished in a mixture with more than 97 % accuracy based on individual blockades. Foetal Hb, which shows a larger sequence variation, was distinguished with near 100 % accuracy. Continuum and Brownian dynamics simulations revealed that Hb occupies two energy minima, one near the inner constriction and one at the trans entry of the nanopore. Thermal fluctuations, the charge of the protein, and the external bias influence the dynamics of Hb within the nanopore, which in turn generates the unique ionic current signal in the Hb variants. Finally, Hb was counted from blood samples, demonstrating that direct discrimination and quantification of Hb from blood using nanopores, is feasible.

Subjects

HEMOGLOBINS; SICKLE cell anemia; AMINO acids; NANOPORES; PROTEOMICS; FETAL hemoglobin

Publication

Angewandte Chemie, 2022, Vol 134, Issue 34, p1

ISSN

0044-8249

Publication type

Academic Journal

DOI

10.1002/ange.202206227