1. Neuroscience
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Possible magneto-mechanical and magneto-thermal mechanisms of ion channel activation in magnetogenetics

  1. Mladen Barbic  Is a corresponding author
  1. Howard Hughes Medical Institute, United States
Research Article
Cite this article as: eLife 2019;8:e45807 doi: 10.7554/eLife.45807
8 figures and 1 additional file

Figures

Genetically engineered construct in magnetogenetics.

Thermo-sensitive or mechano-sensitive ion channel is closely coupled to the iron-loading protein ferritin. External DC or AC magnetic fields are applied in order to influence the ion channel function.

https://doi.org/10.7554/eLife.45807.002
Three distinct spin coupling configurations of iron atoms in ferritin.

(a) Paramagnetic state where N irons spins are magnetically independent from one another and non-interacting. (b) Clusterparamagnetic state where N iron spins are separated into n independent clusters of N/n exchange coupled spins. (c) Superparamagnetic state where all N spins are strongly coupled by the magnetic exchange interaction and behave as a single macro-spin.

https://doi.org/10.7554/eLife.45807.003
Magnetic properties of clusterparamagnetic ferritin.

(a) Ferritin particle magnetic moment vs. magnetic field as a function of different cluster numbers n of N/n exchange coupled spins in a particle of N spins. For the superparamagnetic spin arrangement of Figure 2c (n=1, black curve), the particle moment saturates at relatively low magnetic fields and the magnetic moment is three orders of magnitude higher than for the paramagnetic state of Figure 2a (n = 4500, light blue curve). The curves for the clusterparamagnetic configurations of Figure 2b (n = 5, 15, 45, 450) are also shown. The inset in (a) shows the attractive force configuration between two ferritins. (b) The interaction energy magnitude (E = m·B) of the iron loaded ferritin as a function of the external magnetic field. For modest clustering of iron spins into n clusters of N/n exchange coupled spins the interaction energy is above kBT in moderate magnetic fields. The maximum theoretically possible torque on an anisotropic ferritin particle Γ=mXB, shown diagrammatically in the inset of (b), has interaction energy above kBT.

https://doi.org/10.7554/eLife.45807.004
Diamagnetic force deformation of ion channel and cell membrane.

(a) Diamagnetic ion channel in the cell membrane experiences magnetic fields from the ferritin particle and the externally applied magnetic field B, as well as the large magnetic field gradient from the ferritin particle. This results in the repulsive diamagnetic force on the ion channel and the cell membrane in (b) that is sufficient to potentially mechanically deform them and affect the ion channel function.

https://doi.org/10.7554/eLife.45807.005
Magneto-caloric effect in clusterparamagnetic ferritin.

(a) In zero magnetic field, n clusterparamagnetic moments of N/n exchange coupled spins are randomly fluctuating and have high magnetic entropy. (b) Upon application of external magnetic field B the clusterparamagnetic moments align with the field and have low entropy. In the adiabatic process this change in spin entropy is compensated for by the exchange of energy between the spin ensemble and the magnetite particle lattice. For a given magnetic field B and temperature T, there is an optimal clusterparamagnet size that will generate maximum entropy change and energy transfer to the magnetite particle lattice.

https://doi.org/10.7554/eLife.45807.006
Magneto-caloric energy change for N = 4500 iron atom ferritin particle as a function of the number of clusters n (each with N/n spins) at a physiological temperature T = 310K and several applied magnetic field values B.

For a given applied magnetic field B and temperature T, there is an optimal clustering size n (of N/n spins in each cluster) that will generate maximum entropy change and energy transfer to the magnetite particle lattice. No value of applied magnetic field B is sufficient to achieve magneto-caloric energy change above kBT for a paramagnetic ferritin (n = 4500, Figure 2a). However, grouping of the spins into n exchange coupled clusters (Figure 2b) achieves magneto-caloric energy changes above the kBT level.

https://doi.org/10.7554/eLife.45807.007
Einstein-de Haas effect in ferritin.

(a) Ferritin magnetic moment +m is aligned with the field B and caries mechanical angular momentum of L = +m/ɣ. (b) Magnetic moment reversal to -m results in the total change of angular momentum of ΔL = 2m/ɣ that is compensated for by the mechanical rotation of the particle or by the mechanical torque on the particle.

https://doi.org/10.7554/eLife.45807.008
Magnetic moment fluctuations.

(a) In zero external magnetic field, the ion channel experiences Tesla-scale magnetic fields and large field gradients from the fluctuating superparamagnetic particle moment at GHz-scale frequencies, as well as the corresponding AC diamagnetic forces and torques. (b) In the external field B, the ion channel experiences Tesla-scale DC magnetic fields and large field gradients from the stabilized ferritin magnetic moment, and the corresponding DC diamagnetic forces and torques.

https://doi.org/10.7554/eLife.45807.009

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