Abstract
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.
Highlights
Our cells utilize a set of receptors capable of perceiving physical cues from their environment, which are involved in physiological processes such as touch or nociception and in pathological processes like cardiomyopathies or cancer progression.[1]
The magnetic properties of the iron-containing core are the ones that are relevant for the magnetogenetics application, limiting the forces that can be exerted by the external magnetic field
In these two studies the MNPs lacked a direct targeting to the transient receptor potential vanilloid family member 1 (TRPV1) channels; for in vitro studies, their attachment to the cell membrane relied on surface functionalisation with polyethylene glycol (PEG) to prevent internalisation[111] and with poly(ethyleneimine) to enable membrane binding,[37] while for in vivo experiments MNPs were injected in the brain area in which the TRPV1-expressing neurons were located
Summary
Our cells utilize a set of receptors capable of perceiving physical cues from their environment, which are involved in physiological processes such as touch or nociception and in pathological processes like cardiomyopathies or cancer progression.[1] During the last years, much effort has been devoted to the development of tools for remote manipulation of these cellular functions, using non-invasive stimuli such as light, electricity, ultrasounds or magnetic fields These technologies can contribute to shedding light on our understanding of biological processes, paving the way for the development of exciting tools useful in basic research and clinical applications. The use of smaller magnetic actuators such as ferritin or magnetic nanoparticles (MNPs), with sizes comparable to conventional proteins, permits a specific targeting of cell receptors Such magnetic actuators, in combination with magnetic fields, are emerging as new instruments to precisely manipulate mechanical forces, providing an exclusive approach to the study of mechanotransduction. We will discuss the recent discrepancies that can be found in the literature, highlighting that despite its great potential, there are still many issues that must be resolved before the high expectations initially raised by magnetogenetics can be reached
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