Weak magnetic fields modulate superoxide to control planarian regeneration

Abstract

Reactive oxygen species (ROS) signaling regulates cell behaviors and tissue growth in development, regeneration, and cancer. Commonly, ROS are modulated pharmacologically, which while effective comes with potential complications such as off-target effects and lack of drug tolerance. Thus, additional non-invasive therapeutic methods are necessary. Recent advances have highlighted the use of weak magnetic fields (WMFs, <1 mT) as one promising approach. We previously showed that 200 μT WMFs inhibit ROS formation and block planarian regeneration. However, WMF research in different model systems at various field strengths have produced a range of results that do not fit common dose response curves, making it unclear if WMF effects are predictable. Here, we test hypotheses based on spin state theory and the radical pair mechanism, which outlines how magnetic fields can alter the formation of radical pairs by changing electron spin states. This mechanism suggests that across a broad range of field strengths (0–900 μT) some WMF exposures should be able to inhibit while others promote ROS formation in a binary fashion. Our data reveal that WMFs can be used for directed manipulation of stem cell proliferation, differentiation, and tissue growth in predictable ways for both loss and gain of function during regenerative growth. Furthermore, we examine two of the most common ROS signaling effectors, hydrogen peroxide and superoxide, to begin the identification and elucidation of the specific molecular targets by which WMFs affect tissue growth. Together, our data reveal that the cellular effects of WMF exposure are highly dependent on ROS, and we identify superoxide as a specific ROS being modulated. Altogether, these data highlight the possibilities of using WMF exposures to control ROS signaling in vivo and represent an exciting new area of research.

Radical pairs and superoxide amplification can explain magnetic field effects on planarian regeneration

“…First, we will see whether an RPM-based O -2 production scheme can indeed explain the behavior of magnetic fields on planarian regeneration, as suggested by Kinsey et al For this purpose, we will compare the prediction of our RPM model for O -2 yield with the effects observed by Kinsey et al [34] for 200 and 500 µT exposures 2 hours postamputation. We will look for an agreement regarding the shape of WMF effects between our simulations and empirical observation.…”

“…Unlike previous studies [23, 24], we do not assume H 2 O 2 to be the singlet product as this would contradict the empirical observations. Kinsey et al [34] did not observe any significant effect of WMF on H 2 O 2 concentration.…”

“…). This underlying FH and O -2 based RPM can serve as the basis for explaining various WMF effects observed in the context of for O -2 production [19,34]. However, it should be noted that free O -2 is subject to fast spin relaxation, which can severely affect the magnetosensitivity of such an RP.…”

“…The WMF effects on O -2 levels were significantly greater 2 hours after amputation than 1 hour after. ) for both 200 and 500 µT fields with respect to geomagnetic control after 1 and 2 hours of amputation [34].…”

Biophysics at the edge of life and death: Radical control of apoptotic mechanisms

“…For example, hypomagnetic fields (<5 µT) increased ROS levels in fibrosarcoma cells, but reduced cell survival of mouse skeletal muscle (Martino and Castello, 2011;Fu et al, 2016). It is important to recognize that different MF strengths can have different (and even opposite) effects on ROS levels, even in the same context; 200 µT inhibits while 500 µT increases superoxide levels and regenerative proliferation during planarian regeneration (Kinsey et al, 2023). These effects are consistent with the theoretical model for how MFs exert control at the quantum level to produce cellular changes in intracellular and extracellular ROS generation [mechanisms reviewed in (Zadeh-Haghighi and Simon, 2022)].…”