Biosensors to Probe Amyloidosis-Like Diseases

The focus of this work is on the numerical investigation of the charge transport properties of the de novo-designed alpha3 polypeptide, a 21-residue with three repeats of the seven-residue sequence Leu-Glu-Thr-Leu-Ala-Lys-Ala, as well as its variants (the so-called 5Q-alpha3 and 7Q-alpha3 peptides), all of them probed by gene engineering. The theoretical model makes use of a tight-binding Hamiltonian within the density functional theory approach. We investigate if the biased alpha3 polypeptide and its variants can be identified by charge transport measurements through current-voltage (IxV) curves, as a pattern to characterize their fibrous assemblies. We found that, from their IxV profiles, the alpha3 peptide, that has the most fibrous assemblies, shows the smaller current saturation; the 5Q-alpha3 variant, which forms fibrous assemblies more attenuated than those of the alpha3 peptide, has a current saturation higher than alpha3, but smaller than 7Q-alpha3; finally, the 7Q-alpha3 variant does not form fibrils and shows the highest current saturation, suggesting that charge transport in peptides can turn out to be a useful tool for the development of biosensors to probe the onset of amyloidosis-like diseases. We hope that this biomedical application of the charge transport in proteins and polypeptides should stimulate experimental and engineering technological developments.