Abstract

Developing synthetic biological devices to allow the noninvasive control of cell fate and function, in vivo can potentially revolutionize the field of regenerative medicine. To address this unmet need, we designed an artificial biological “switch” that consists of two parts: (1) the electromagnetic perceptive gene (EPG) and (2) magnetic particles. Our group has recently cloned the EPG from the Kryptopterus bicirrhis (glass catfish). The EPG gene encodes a putative membrane-associated protein that responds to electromagnetic fields (EMFs). This gene’s primary mechanism of action is to raise the intracellular calcium levels or change in flux through EMF stimulation. Here, we developed a system for the remote regulation of [Ca2+]i (i.e., intracellular calcium ion concentration) using streptavidin-coated ferromagnetic particles (FMPs) under a magnetic field. The results demonstrated that the EPG-FMPs can be used as a molecular calcium switch to express target proteins. This technology has the potential for controlled gene expression, drug delivery, and drug developments.

Highlights

  • Various methods of expressing a target protein using external stimuli have been studied

  • The final result is the expression of the target genes/proteins in cells represented as output in the circuit

  • It is confirmed that the electromagnetic perceptive gene (EPG) is related to the control of Ca ion channels but the exact pathway is unknown

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Summary

Introduction

Various methods of expressing a target protein using external stimuli have been studied. Target proteins have been quantitatively expressed by external stimuli such as the control of substrate (isopropyl β-d-1-thiogalactopyranoside; IPTG) [7], temperature [8], nutrients [9], oxygen [10], and growth factors [11]. These controls take advantage of allosteric regulators, temperature, and growth factors used for normal protein expression. These are not the methods of expressing target proteins by active control that can be turned on or off by an external magnetic field. An alternative method that involves using a biological on/off switch as stimulus is desirable [14,19]

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