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Bioelectromagnetism

the thermal energy, kBT (Hiscock et al., 2019). By means of this lower bound, Ren et al. (2021) showed

how the performance of the compass sense could be optimized by adjusting the orientation of CRY

molecules within photoreceptor cells, the distribution of cells around the retina, and the efects of the

GMF on the photochemistry of the radical pair. Teir results indicated how the precision of this com­

pass could be optimized to make the best use of the relatively small number of photons available to these

nocturnal migrants (Ren et al., 2021).

Xu et al. (2021) speculated that CRY4 molecules are not expected to show substantial responses to the

GMF strength in vitro unless they are anchored, aligned, and associated with the appropriate signal­

ing partners. None of the proteins required for these interactions is currently known (Wu et al., 2020).

Furthermore, magnetic sensitivity could be enhanced by receptor alignment (Efmova and Hore, 2008),

biochemical amplifcation (Wu et al., 2020), and neural processing (Zapka, 2009). Tese aspects can

also be optimized by evolution and could substantially improve the magnetic sensitivity of the robin’s

magnetic sense (Xu et al., 2021).

Xu et al. (2021) showed that the photochemistry of CRY4 from the night-migratory European robin

(Erithacus rubecula) (ErCRY4) is magnetically sensitive in vitro, and more so than CRY4 from two

non-migratory bird species, chicken (Gallus gallus) and pigeon (Columba livia). Site-specifc muta­

tions of ErCRY4, which is a protein that is expressed in double-cone and long-wavelength single-cone

photoreceptor cells in the eyes of night-migratory European robins (Günther et al., 2018), revealed the

roles of four successive favin-tryptophan (Trp) radical pairs in generating magnetic feld efects and in

stabilizing potential signaling states in a way that could enable sensing and signaling functions to be

independently optimized in night-migratory birds (Xu et al., 2021). To determine whether CRY4 acts as

a magnetoreceptor molecule in vivo, direct manipulations of this protein in the eyes of night-migratory

songbirds would be required (Xu et al., 2021).

To explain the biological efects of weak magnetic felds, some molecular transduction mechanisms

have been proposed (Binhi and Prato, 2018; Bialas et al., 2019). While for animal navigation/orientation,

the main hypothesis is a specialized magnetic sense associated with pairs of radicals located in the ret­

ina of the eye, nonspecifc efects could occur due to the interaction of magnetic felds with the magnetic

moments of rotating molecules dispersed in the organism. Indeed, Binhi and Prato (2018) have shown

that the precession of the magnetic moments of these rotating molecules can be slowed due to a mixing

of the quantum levels of magnetic moments called the “Level Mixing Mechanism (LMM)” inducing a

magnetic feld dependence that is in good agreement with experiments in which biological efects arise

in response to the reversal of the magnetic feld vector.

Te RPM-mediated magnetic feld efects emerge from the anisotropic hyperfne interactions between

the radicals’ electron spins and associated nuclei (Schulten et al., 1978; Ritz et al., 2000). Tese interac­

tions can govern the spin dynamics when inter-radical interactions, such as the dipolar and exchange

interactions, are small (Hiscock et al., 2016b) or mutually balanced (Efmova and Hore, 2008). Radical-

radical couplings generally inhibit magnetosensitivity at low felds by lifing the zero-feld degeneracy

of singlet and triplet states, thereby impeding feld-dependent singlet−triplet conversion, and also by

inducing spin relaxation (Timmel et al., 1998; Kattnig et al., 2016).

Furthermore, recent calculations showed that electron-electron dipolar (EED) interactions can abol­

ish the “quantum needle,” a sharp feature in the directional magnetic feld efect that was predicted to

boost the acuity of the compass (Hiscock et al., 2016b, 2017), and may nullify the Larmor resonance

(Hiscock et al., 2016a, 2017), which is a phenomenon observed in some behavioral studies employing

radiofrequency (RF) magnetic felds to test for the RPM (Ritz et al., 2009). Nonetheless, the majority

of past theoretical works on CRY-mediated magnetoreception have omitted EED coupling to facilitate

calculations on spin systems too large to be treated otherwise, instead of focusing on hyperfne-induced

efects as the sine qua non of low feld magnetic feld efects (Hiscock et al., 2016b; Atkins et al., 2019).

Tus, prior studies have ofen neglected the EED coupling from this hypothesis. By simulating the

radical pair models, Babcock and Kattnig (2020) showed that EED interactions suppress the anisotropic

response to the GMF by the RPM in CRY, and that this attenuation is unlikely to be mitigated by the