Magnetogenetics: remote activation of cellular functions triggered by magnetic switches

During the last decade, the possibility to remotely control intracellular pathways using physical tools has opened the way to novel and exciting applications, both in basic research and clinical applications. Indeed, the use of physical and non-invasive stimuli such as light, electricity or magnetic fields offers the possibility of manipulating biological processes with spatial and temporal resolution in a remote fashion. The use of magnetic fields is especially appealing for in vivo applications because they can penetrate deep into tissues, as opposed to light. In combination with magnetic actuators they are emerging as a new instrument to precisely manipulate biological functions. This approach, coined as magnetogenetics, provides an exclusive tool to study how cells transform mechanical stimuli into biochemical signalling and offers the possibility of activating intracellular pathways connected to temperature-sensitive proteins. In this review we provide a critical overview of the recent developments in the field of magnetogenetics. We discuss general topics regarding the three main components for magnetic field-based actuation: the magnetic fields, the magnetic actuators and the cellular targets. We first introduce the main approaches in which the magnetic field can be used to manipulate the magnetic actuators, together with the most commonly used magnetic field configurations and the physicochemical parameters that can critically influence the magnetic properties of the actuators. Thereafter, we discuss relevant examples of magneto-mechanical and magneto-thermal stimulation, used to control stem cell fate, to activate neuronal functions, or to stimulate apoptotic pathways, among others. Finally, although magnetogenetics has raised high expectations from the research community, to date there are still many obstacles to be overcome in order for it to become a real alternative to optogenetics for instance. We discuss some controversial aspects related to the insufficient elucidation of the mechanisms of action of some magnetogenetics constructs and approaches, providing our opinion on important challenges in the field and possible directions for the upcoming years.