Thomas Heimburg, who works at the Niels Bohr Institute in Copenhagen, is a physicist who studies quantum mechanics and biophysics. However, he hopes to overturn many textbooks in neuroscience. In Hömberg's view, neurons communicate via mechanical waves similar to sound waves, and electrical pulses are only a by-product of this process. If Humber's theory is confirmed, it will fundamentally change biology. The cover story of the latest issue of Global Science tells us this incredible study.
"misguided" scientists
For many years, scientists have been trying to understand nerve impulses. It only lasts a few moments. It takes less than one second from the time you walked on a thumbtack to your brain to receive a pain signal. The speed of transmission of the signal along the nerve fibers is approximately 30 m/s.
Around the 1950s, researchers mastered the technique of measuring the potential difference inside and outside the cell membrane. They found that when the signal passes along the nerves through the electrodes, the membrane potential changes drastically within a few milliseconds. In 1952, two British scientists, Alan Hodgkin and Andrew Huxley, discovered that when neurons were excited, sodium ions poured from the cell membrane into the cell membrane; then, potassium ions Fluctuations from the cell membrane outside the cell membrane, so that the membrane potential returned to normal. The Hodgkin-Huxley model they proposed became the cornerstone of modern neuroscience.
Hodgkin-Huxley model diagram
Hodgkin and Huxley won the Nobel Prize in 1963, but there are still some scientists looking for experimental phenomena that are inconsistent with the model. But in the past, these scientists were thought to be in the wrong direction and did not receive attention.
One of them is Ichiji Tasaki, a neurobiologist at the National Institutes of Health (NIH). Tasaki 12 received a doctorate from Keio University in Japan in 1938 and traveled to the United States in 1951, joining the NIH shortly thereafter. Tasaki was famous in the neuroscience community for his discovery of the action potential jump conduction on the lang fei's knot (where nerve fiber is not surrounded by an insulating myelin sheath), but in 1979 he made a challenge to the traditional experiment: anatomy. The leg of the crab exposed a nerve and carefully placed a small piece of reflective platinum on the microscope, followed by a laser beam to illuminate the platinum sheet. By measuring the reflection angle of the laser, he can detect if the width of the nerve bundle changes slightly when the action potential passes. He and his then postdoctoral fellow Kunihiko Iwasa conducted hundreds of measurements. A week later, the data clearly showed that when the action potential passed, the nerve bundles would become slightly wider and narrower. The whole process was only a few milliseconds.
Although the magnitude of the deformation is small, the surface of the cell membrane only rises by about 7 nm, but this phenomenon is completely consistent with the rhythm of the passing electrical signals, confirming the speculation over the years that Tian Zaki has: Hodgkin and Huxley’s proposed theory is not necessarily correct.
Tasaki believes that the neural signal is far more than just an electrical signal. It is also a mechanical signal. If you only use electrodes to measure nerve cells, you will miss a lot of important information.
In efforts to find evidence, Tasaki gradually deviated from the academic mainstream. Other factors make his situation more difficult. He was born in Japan and his English is not fluent. “You need to know a lot of information beforehand to be able to have an in-depth conversation with him,†said Peter Basser, director of the NIH Department of Neuroscience and who has known Tasaki for more than 20 years. “And I know many people think that his opinion is already It's not as deep as when I was young.†On the other hand, although Tasaki and many visiting scientists have cooperated, he himself has not developed a disciple who can inherit the clothes.
Tasaki Taro and his wife Photo credit: irp.nih.gov
In an NIH reorganization in 1997, Tasaki closed his own laboratory and moved to a small place where the Bache lab was located. He continued working seven days a week until he was in his 90s. One day in December 2008, when he walked around his home, he suddenly lost his balance and his head fell to the ground. One week later he died at the age of 98.
At that time, Tasaki's work had already disappeared from people's perspective. Adrian Parsegian, a biophysicist from the University of Massachusetts Amherst, who has been working at NIH from 1967 to 2009, said, “I don’t think anyone has questioned Those phenomena exist because Tasaki is very respected in the laboratory." But people think that the discovery of Tasaki is not the essence of neural signals, but more of a byproduct of electrical signals. "The real scientific problem has not been solved," Pasigian said. "The same thing goes into textbooks, and the other side doesn't."
Is neural signal a mechanical wave?
In the mid-1980s, Humbert was studying for a doctorate at the Max Planck Institute for Biophysical Chemistry in Germany. At that time, he was exposed to the work of Tasaki. He was fascinated by this problem all of a sudden, and he read the ancient literature in the library all day. Unlike Tian Tianqi's theory, Humbert found another way to explain experimental phenomena. He believes that mechanical wave, changes in optical properties, and transient thermal effects originate from the nerve's cell membrane of lipids rather than proteins and carbohydrate fibers underneath the cell membrane.
Thomas Heimburg Photo credit: Niels Bohr Institutet
Humbert immediately began his own experiment—by compressing artificial cell membranes and studying their response to mechanical shock waves. His research has found some important findings: the oily lipid molecules that make up the cell membrane can usually flow and have a random orientation, but are prone to phase transitions (a process in which a substance changes from one phase to another phase). As long as the cell membrane is gently squeezed, the lipid molecules immediately condense into a highly ordered liquid crystal state.
According to these experiments, Humber inferred that nerve impulses are mechanical shock waves that propagate along the nerve cell membrane. When the shock wave propagates, the liquid membrane molecules are squeezed into liquid crystals, releasing a little heat during the phase transition, just like water forms ice. Then, when the shock wave passes, the cell membrane changes back to liquid state and absorbs heat. The entire process takes several milliseconds. The transient phase transition made the cell membrane slightly wider, as observed by Tasaki and Iwasaki when they were irradiated with laser light on the platinum sheet.
Textbooks usually depict the cell membrane as a thin layer of insulation. But now, physicists are beginning to realize that the cell membrane has amazing properties. It belongs to a class of materials called piezoelectric bodies in which mechanical and electrical energy can be transformed into one another. The physics of quartz watches is based on this. This means that the voltage pulse on the cell membrane also carries mechanical waves, and mechanical waves may also appear as voltage pulses.
The experimental evidence of this theory was found by Humbert's former students. In 2009, Matthias Schneider, a biophysicist at the Technical University of Dortmund in Germany, discovered that applying a voltage pulse to an artificial cell membrane can trigger a mechanical wave. His pulse intensity is similar to that of nerve cells. The shock wave is generated at a speed of about 50 m/s, which is similar to the speed at which nerve signals travel in the body. In 2012, Schneider also confirmed that mechanical waves and voltage pulses are different parts of the same wave that travels on the membrane.
However, Schneider’s most important discovery was in 2014. A key feature of nerve impulses is "all or nothing." If the nerve cell receives a stimulus below a certain threshold, it will not produce any response. Only when the input is strong enough, the cells will be discharged. Schneider found that the electro-mechanical waves on the surface of artificial cell membranes are also “all or nothingâ€. Whether the cell membrane is under sufficient pressure to enter the liquid crystal state seems to be a factor that determines the generation of electro-mechanical waves. "Only in this case," Schneider said, "you can observe nerve impulses."
Highly controversial
Humbert named his theory "soliton theory" (solitary wave refers to a wave that maintains its shape in the process of transmission), but so far the attitude of the biology community has frustrated him. His theory was first published in the 2005 Proceedings of the National Academy of Sciences (PNAS). Although the magazine has a high reputation in the academic world, criticism of him has been since then. Did not stop.
Catherine Morris, a well-known neurobiologist who has retired from the Ottawa Hospital Research Institute in Canada, was one of the skeptics. She told me that Humbert’s research office revealed that he thought it was easy The arrogance of physicists into other fields to correct others' misconceptions. Her feelings can be summed up in her favorite words: "What I heard was typical physicist argument - 'We can approximate this cow as a point'."
Morris's reaction is understandable to some extent. Because it is thought that the nerve signal is both a mechanical wave and an electrical pulse, but as Humbert and Schneider asserted, the ion channel has no role in the process of nerve conduction is another matter. This is the worst and most erroneous disagreement between Humber and Schneider's theory and mainstream opinion. You know, scientists have discovered hundreds of ion channel proteins. They also know that drugs can selectively regulate ion currents, and they can also modify the genes corresponding to these proteins to control the discharge of nerve cells. "They actually turned a blind eye to so much biological evidence," said Maurice, who studied ion channel proteins for 30 years.
Humbert and Schneider's questioning of traditional concepts embodies a kind of "culture" of physics - it is believed that all phenomena can be explained by thermodynamic principles. In their opinion, biologists only care about proteins and ignore these principles. Tasaki also has similar minimalist beliefs, which may be one of the reasons why his theory is not valued.
Brian Salzberg, who studied neurophysics at the University of Pennsylvania who had an intersection with Tasaki, said, “Tatsuki is a very smart experimenter, and I have no doubt about what he measured (neural width). The change is real, but his interpretation of the result is wrong.†Zarzberger said that the reason why the nerve fibers transiently widen when the voltage pulse passes is partly due to the crossover of sodium and potassium ions. As the membrane flows, some water molecules also enter and exit the cell membrane through ion channels. If Tianqi can accept the concept of ion channels, he may be open to other explanations of mechanical waves.
Nobel Prize found?
When the nerve signal is generated, the generated heat energy can reach twice the electric energy, but the latter completely dominates the neuroscience research. The part of the signal that has nothing to do with electricity has not been favored by researchers. Part of the reason can also be attributed to historical accidents.
Tasaki is a talented instrument maker who, after coming to the United States, used his skills to create an exquisite one-off device that can measure the instantaneous changes in the heat and size of nerve cells.
However, these equipment and experimental skills did not eventually spread across other groups of scientists. Scientists have found simpler measurement methods, such as patch clamp techniques that measure the potential of a single neuron. With the widespread dissemination of these experimental techniques, the concept of understanding neural signals as electrical signals has become increasingly popular. Pasaijian admits, "This is a cultural bias. People usually look for tools they can understand and avoid those tools that are difficult to understand. This may have an impact on thinking."
The situation of Humber and Schneider today is delicate. They may be awarded the Nobel Prize, or they may be trapped and obscured by his own attachment as Tasaki. But in February of this year, Humbert insisted to me: "Many people just want to repair the Hodgkin-Huxley model with our theory. However, I personally cannot accept any compromise between these two theories."
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