Magnetic entropy as a gating mechanism for magnetogenetic ion channels

Abstract

Magnetically sensitive ion channels would allow researchers to better study how specific brain cells affect behavior in freely moving animals; however, recent reports of "magnetogenetic" ion channels have been questioned because known biophysical mechanisms cannot explain experimental observations. Here we show that magnetic fields can produce a change in the magnetic entropy of biogenic nanoparticles, which in turn may generate sufficient heat to gate temperature-sensitive ion channels. This magnetocaloric effect provides a rational approach for developing future magnetogenetic channels.

Electromagnetic Regulation of Cell Activity

“…When the construct was expressed in striatal dopamine receptor 1-expressing neurons, neurons that are known to be involved in reward behavior, mice showed greater preference for the region of a chamber treated with a magnetic field. The ability of the Magneto 2.0 construct to regulate cell activity in vitro has also been confirmed by other investigators (Duret et al 2017).…”

“…Because the conductance of TRP channels is relatively high (TRPV1 95-103 picosiemens [Cheng et al 2012], TRPV4 60 picosiemens [Strotmann et al 2000]) compared with channelrhoposin (50 femtosiemens [Nagel et al 2003]), opening this proportion of channels in a neuron or HEK cell would lead to detectable calcium influx and depolarization. Supporting their theoretical calculations, Duret et al (2017) show that the calcium response to magnetic field treatment is lost in cells expressing a temperature-insensitive TRPV4-ferritin construct. Similarly, Hutson et al (2017) show that the calcium response to oscillating magnetic field treatment is also lost in cells expressing a temperature-insensitive TRPV1 fused to a ferritin-binding domain.…”

“…Electromagnetic fields can penetrate tissue and in birds and other animals will guide migration, although the precise mechanism is unknown (Freake et al 2006). More recently, it has been shown that electromagnetic fields can be used to regulate the activity of cells in proximity to external metal nanoparticles (Huang et al 2010;Chen et al 2015), or that express genetically encoded intracellular metal nanoparticles (ferritin) (Stanley et al 2015;Wheeler et al 2016;Duret et al 2017;Hutson et al 2017). In both cases, the particles transduce electromagnetic fields that gate ion channels, although the field strength that is required is much larger than that required for magnetic sensing by biologic systems.…”

“…Theoretical calculations (Meister 2016) suggest that static or oscillating magnetic fields acting on ferritin would not generate sufficient mechanical force or heat to open the associated channel via classical mechanisms. However, recent theoretical work supported by experimental findings suggest an alternative mechanism based on the magnetocaloric effect (Duret et al 2017). Duret et al propose that in the absence of a magnetic field, the magnetic moments in ferritin are orientated in a random fashion and therefore have high magnetic entropy.…”

Evaluating Methods and Protocols of Ferritin-Based Magnetogenetics

“…Incubating cells at 37 o C over extended periods of time may contribute to TRPV4 recycling. To examine if abolishing the temperature sensitivity of TRPV4 FeRIC prevents its functional downregulation, we used the temperature-insensitive mutant TRPV4 DTFeRIC (Y555A/S556A) (Duret et al, 2019;Hernández-Morales et al, 2020;Voets et al, 2002). RF stimulation significantly increased the GCaMP6 fluorescence in TRPV4 DTFeRIC -expressing N2a cells imaged at either 24 or 72-h post-transfection compared with unstimulated cells ( Fig.…”