Despite ample evidence that it does occur, electron tunneling related to ferritin was first hypothesized in 1988. However, this idea is still considered with skepticism today. My co-authors and I recently reviewed the evidence of electron tunneling in ferritin as well as the evidence that such electron tunneling may be utilized by biological systems such as the retina, the cochlea, macrophages, glial cells, mitochondria, and magnetosensory systems in our paper that was recently published in IEEE Transactions on Molecular, Biological, and Multi-Scale Communications.
We hope that this article will increase understanding of the mechanism of electron tunneling associated with ferritin and encourage the additional study of that phenomenon in biological systems that contain ferritin, especially in cases where there isn’t a clear need for it.
A brief history of Ferritin and ferritin research
A protein called ferritin, which stores iron, can hold up to 4,500 iron atoms in an 8-nanometer-diameter core and self-assembles into a 12-nanometer-diameter spherical shell that is 2 nanometers thick. It could seem very old with an evolutionary history that seems to go back more than 1.2 billion years, but it should be remembered that single-celled organisms are thought to have originally emerged some 3.5 billion years ago. As a result, the evolution of ferritin may have taken more than 2 billion years. Members of the ferritin family of proteins were probably present when the first multicellular organisms developed around 600 million years ago, and they are still present in practically all plants and animals today.
Eight years after the discovery of quantum dots, semiconductor nanoparticles that behave like artificial atoms and are comparable in size to ferritin, and 88 years after the discovery of quantum mechanics, the first hypothesis that ferritin might possess some quantum mechanical properties was made in 1988. Electron tunneling and magnetic behavior, which result from the way iron crystallizes in the center of the ferritin shell, are examples of quantum mechanical phenomena.
Substantial proof that these quantum mechanical features exist is provided by the subsequent studies detailed in the text. But rather than being thought of as a quantum biological actor, those characteristics in this billion-year-old biostructure seem to have primarily been seen as a curiosity or artifact. Although many of the scientists who discovered quantum mechanics more than 100 years ago thought it could be applied to biology, biologists and many other scientists have viewed the study of quantum biology with skepticism. Nevertheless, the field is expanding and research is being done at many prestigious universities, including Caltech, Yale, the University of Chicago, and UCLA.
What is electron tunneling?
According to quantum mechanics, the physical characteristics of electrons, protons, neutrons, and other so-called “particles” at the subatomic level are characterized in terms of probability waves. These particles exhibit wave-like activity, which has been demonstrated through experiments and is widely acknowledged. These tests characterize those waves as a likelihood of detecting a particle’s physical characteristic at a specific position in time and space, a phenomenon frequently referred to as the “collapse” of the wave function.
However, other than how the wave function behaves, nothing about the particle changes as it collapses. When a wave function behaves as predicted by the Schrödinger wave function, it is said to be “coherent,” however when it interacts with other particles and ceases to behave as predicted by that wave function, it is said to be “incoherent.”
At ambient temperature, the spatial wave-like characteristics of electrons in a vacuum can have a wavelength of approximately 5 nanometers, which is important for molecular interactions. Under the right circumstances, an electron can “tunnel” between molecules, which means that it can appear to move from one molecule to another molecule in a way that is not permitted by adiabatic or classical behavior. This happens when electrons “touch” each other (recognizing that the wave functions of the atoms and sub-atomic particles in the molecules are what is actually interacting). This is just an intrinsic property of electrons; there is nothing unusual about it. However, because the wave function is a probability wave,
Some of my co-authors have demonstrated that electrons seem to tunnel through ferritin for distances of up to 12 nm in successive tunneling events, and they have suggested that the peculiar magnetic properties of the ferritin’s core components may be connected to this exceptionally long electron tunneling distance. That research was founded on “solid-state” studies, which exclude the use of biological systems with living organisms. Electron tunneling must be inferred from other data, such as measured currents and voltages because it cannot be directly detected. Finding proof of such electron tunneling in biological systems can be more challenging, but it is not impossible.
Electron tunneling in biological systems containing ferritin
The electron tunneling in ferritin has been linked to a number of biological reactions. Storage of electrons comes first. The ability of ferritin in solution with water to store electrons for several hours has been established in laboratory testing outside of cells, which is commonly referred to as “in vitro” for the Latin phrase meaning “in the glass.” This is surprising since it would be expected that the ferritin, which stores iron, would immediately release the iron upon receiving an electron, but that does not happen right away. This finding suggests that electrons travel electrochemically or through tunneling rather than being easily carried through the insulating protein layer by classical conduction.
It is also possible that the electrons stored inside the ferritin core can tunnel to molecules outside of the 2-nanometer-thick protein shell, such as free radicals that have energy levels that allow them to receive electrons. Evidence also suggests that electrons can tunnel distances of up to 8 nanometers in a single tunneling event through the ferritin in solid-state tests. One of the roles of antioxidants is to neutralize free radicals by providing an electron in order to prevent them from damaging cells by stealing electrons from other molecules.
In a cellular setting, ferritin interacts with antioxidants like ascorbic acid (often referred to as vitamin C) to stabilize the stored iron. It is also overexpressed in reaction to free radicals. By enabling the electrons to reach free radicals that are farther away and by storing the electrons until they are needed, ferritin could increase the effectiveness of that neutralization reaction if it is able to store antioxidant electrons so they are available to free radicals through electron tunneling.
If the sole purpose of ferritin is to store iron, then it would not make sense when, as is frequently the case, excess iron is not the cause of free radicals, inflammation, or ROS. Iron homeostasis, the intricate process by which cells utilize iron, has made it challenging to pinpoint the electron tunneling that is connected to ferritin.
Electron transport over cellular distances is another suggested quantum biological use for ferritin’s electron tunneling. Ferritin can form rather regularly arranged structures in a type of cell called an M2 macrophage, which the macrophages appear to use to supply ferritin to a cell that the macrophage is assisting.
However, in the lack of antioxidants in those cells, is it feasible for electrons to tunnel through the ferritin structures in M2 macrophages into ferritin in other cells? Antioxidants may also aid some cancer cells to survive by delivering electrons to neutralize free radicals and ROS. That function has also been demonstrated.
Dr. Olga Mykhaylyk used small angle neutron scattering (SANS) experiments on placental tissue containing macrophages and found that there was increased neutron scattering that wasn’t present in the bulk ferritin that was removed from the tissues. These experiments show that ferritin in placental tissue containing macrophages contains aligned magnetic moments, which can cause neutron scattering in solids containing nanoparticles with aligned magnetic moments.
SANS tests were also conducted on self-assembled monolayers (SAMs) of ferritin by Prof. Heinz Nakotte that demonstrated neutron scattering, and tests that I conducted with Prof. Cai Shen showed that self-assembled multilayers of ferritin similar to those in M2 macrophages were not only able to conduct electrons over distances as great as 80 microns in vitro but were also able to route those electrons using a physical mechanism known as a Coulomb blockade.
Another hypothesized quantum biological role involves sending electrons to ferritin, where they are required for the removal of free radicals, inflammation, and ROS in cells. However, as electron tunneling cannot be directly detected, further research is required to test this idea.
Conclusion and next steps
It will be up to researchers in the various fields of study for those biological systems to design tests and to investigate whether electron tunneling is taking place. This new paper in IEEE Transactions provides more information on how these building blocks of electron tunneling functions could be used in various biological systems that contain ferritin.
It may take decades before these concerns are resolved and used to create cures for cancer, blindness, deafness, and other afflictions because many biologists do not comprehend electron tunneling and are dubious about quantum biology. This work aims to contribute to the understanding of whether and how biological systems make use of the well-known phenomena of electron tunneling in ferritin.
This post is a part of Science X Dialog, a platform for researchers to share insights from work that has already been published. For details on ScienceX Dialog and how to take part, see this website.