Cryptochromes (CRYs) are flavoproteins sensitive to weak magnetic fields (MF) in the milli Tesla range. This magnetic sensitivity arises from the intramolecular spin-correlated radical pair (RP) that forms between the flavin adenine dinucleotide cofactor and tryptophan residues upon blue light excitation of CRY. While the RP mechanism has been characterized previously, the biological pathways and effects downstream of the RP mechanism remain poorly understood. Previously, we have demonstrated that lysosomal fusion driven by LAMP-CRY2 oligomerization can be modulated by MF at the scale of tens of mT mediated by RP. This work unlocks new possibilities for the analog control of cell behavior, as numerous intracellular signaling pathways are triggered by molecular oligomerization. Simultaneously triggering different signaling pathways via multiplexing different CRY2-facilitated oligomerizations would provide powerful control over cellular behaviors. To explore this possibility, we built on our LAMP-CRY2 model system by co-expressing both LAMP-CRY2 and cytoplasmic CRY2 in mammalian cells. This new system afforded us to study complex oligomerization patterns under blue light with or without the presence of an external MF. Our results suggest that CRY2 in different subcellular compartments oligomerizes in an orthogonal manner, independent of each other. Moreover, the results imply there might be a critical oligomer size of CRY2, above which a steric hindrance will be imposed on the oligomerization of the orthogonal CRY2-tagged molecules. This study demonstrates the potential of CRY2-tagged molecules to be used as quantum actuators to control multiple aspects of cell behavior.
Chen et al. (Sun,) studied this question.