Visible only under a very high-resolution light microscope, the dynamic waves are made of a signaling protein that directs cell movement. This protein and a second key player were already known to trigger cells to move, but their interaction to generate the self-sustaining waves has now been revealed.
"Seeing the wavelike dynamics of this protein, Hem-1, for the first time was easily the most instantly thrilling and illuminating finding in my scientific career," says Orion Weiner, PhD, of the University of California, San Francisco, who led the scientific team. "It immediately suggested how this protein might be organizing cell movement - an idea that our subsequent experiments validated.
"We never expected to see this sort of complex behavior within cells, but in retrospect it is an absolutely ingenious way to organize cell movement. We're getting our first glimpses that take us beyond knowing that this protein is important for cell motility to learning how it might organize the complex choreography of cell movement."
The videotape of the unsuspected action shows wave upon wave advancing like a series of exploding fireworks. The novel behavior can be viewed at cvri.ucsf.edu/~weiner.
The research findings are reported in the August 13, 2007 online edition of the journal "Public Library of Science (PLoS) Biology." Lead author is Weiner, who is assistant professor of biochemistry at UCSF.
Because the same kind of components scrutinized in the new research also drive cancer cell metastasis, the finding may lead to strategies to block cancer growth. Similarly, faulty regulation of white blood cell movement plays a role in heart attack - another promising target for applying the new insights of the regulation of cell movement, the authors say.
White blood cells, or neutrophils, are the body's first line of defense against potentially harmful microbes, and are one of the swiftest cells in the body. The wave action that speeds them along is generated by the same kind of three-part circuit that fires electrical signals along a neuron or prods the heart to beat, the researchers observe.
Videotaping allowed the scientists to watch as wave upon wave of the Hem-1 protein push neutrophils toward a chemical signal made by invading microbes. The researchers fluorescently tagged Hem-1 to view its dynamic propulsive power under the microscope.
Self-generating waves of Hem-1 control the pattern of assembly of building blocks of a second protein, actin. This protein physically contacts the cell membrane and prods it forward. But actin is not only an output of Hem-1 action; it also appears to eliminate the Hem-1 that has assembled it, the new research shows. The scientists think that this cycle of Hem-1 propulsion and annihilation is likely to produce the series of waves seen under the microscope.
The cell-propelling circuit contains a third component that makes it self-sustaining. The researchers found evidence that before each Hem-1 protein is eliminated, it recruits an additional Hem-1 right "next door." As each Hem-1 succumbs, a new one appears - but only on one side. Weiner thinks the structure of actin physically blocks Hem-1 from recruiting its daughter Hem-1 on one side, so Hem-1 is sequentially added only in one direction. This determines the direction of cell movement.
Weiner likens it to a Lego tower on its side. "If you kept adding blocks to one end and removing them from the other, you would have a moving tower that was the same size but kept adding new material. This is very similar to what is going on in a Hem-1 wave," he says.
The Hem-1 recruitment assures the cycle will continue. The cycle, or circuit, of activation, recruitment and inhibition, as it is called, can continue without "orders" from another part of the cell, the scientists report.
"One of the things that I find fascinating about these waves is how relatively simple patterns of protein interaction can generate very complex behaviors," says Weiner. "Evolution has found the same solution to generating waves again and again even with completely different molecules, and at different scales of space and time -- encouraging for those of us who want to uncover general organizing principles in biology."
Weiner is an investigator in both the UCSF Cardiovascular Research Institute and the California Institute for Quantitative Biosciences, or QB3, headquartered at UCSF.
Weiner initiated the research as a postdoctoral fellow in the lab of Marc Kirschner, PhD, professor and chair of systems biology at Harvard Medical School. Kirschner is a co-author on the paper.
The cycle the scientists studied is very similar in concept to the circuit that generates neuronal conduction, the beating of the heart, and many other waves in biology, according to Weiner.
"All of these use a self-activating signal that plants the seeds for its own destruction, even while it is progressing. This results in a wave that moves undiminished because of the self-activation, and in one direction, because of the inhibition it leaves in its wake," he says.
The scientists observed the Hem-1 activation of actin assembly and actin's inhibition of Hem-1 accumulation. The "recruitment" component was not directly observed, but is consistent with their observations and experiments.
In the research, the team used the fluorescently tagged Hem-1 to determine whether the protein participated in the wave action, or was the wave itself.
Using optical tricks to label specific pools of Hem-1, they found that molecules of Hem-1 don't move, but pass information between molecules to generate a wave.
The research is now focusing on how external signals influence this wave generator to guide the cells. They also want to learn if the wave action they have discovered in neutrophils also controls movement and shapes changes in other cells and organisms.
Wallace Ravven | EurekAlert!
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences