Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning

Version 1 : Received: 23 August 2021 / Approved: 25 August 2021 / Online: 25 August 2021 (10:39:42 CEST)
Version 2 : Received: 17 September 2021 / Approved: 17 September 2021 / Online: 17 September 2021 (11:58:04 CEST)
Version 3 : Received: 1 October 2021 / Approved: 1 October 2021 / Online: 1 October 2021 (11:12:13 CEST)

A peer-reviewed article of this Preprint also exists.

Yang, D.-M.; Chang, Y.-F. Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning. Biosensors 2021, 11, 371. Yang, D.-M.; Chang, Y.-F. Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning. Biosensors 2021, 11, 371.

Abstract

The heavy metal lead (Pb) can irreversibly damage the human nervous system. To help understand Pb-induced damage, we have developed practical applications for genetically encoded Pb biosensors in cardiac cells and insect central nervous tissue. We applied the optimized fluorescence resonance energy transfer (FRET)-based Pb biosensor Met-lead 1.44 M1 to two living systems to monitor the concentration of Pb: induced pluripotent stem cell (iPSC)-derived cardiomyocytes as a semi-tissue platform, and Drosophila melanogaster fruit flies as an in vivo animal model. Different FRET imaging modalities were used to obtain FRET signals, which repre-sented the presence of Pb in the tested samples in different spatial dimensions. Pb was effectively sensed in two living models producing Met-led 1.44 M1. In iPSC-derived cardiomyocytes, the relationship between beating rate determined from the fluctuation of fluorescent signals and the concentrations of Pb represented by the FRET emission ratio values of Met-lead 1.44 M1 demonstrated the potential of this fluorescence biosensor system for anti-Pb drug screening. In the Drosophila model, Pb was detected within the adult brain or larval central nervous system using fast epifluorescence and high-resolution two-photon 3D FRET ratio image sys-tems. The optimized Pb biosensor together with FRET microscopy can be used for specific applications to de-tect Pb with a limit of detection of 10 nM (2 ppb). We believe that this integrated Pb biosensor system can be applied to the prevention of Pb poisoning.

Keywords

Drosophila melanogaster; fluorescence resonance energy transfer; Met-lead 1.44 M1; Pb biosensor

Subject

Biology and Life Sciences, Biology and Biotechnology

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