Nav: Home

Powerful microscope captures first image of nanoscaffold that promotes cell movement

January 11, 2019

LA JOLLA, CALIF. - Jan. 11, 2019 - There are many times when our cells need to move. Mobile cells guide our body's formation (embryonic development). Immune cells roam to capture unwanted intruders. And healing cells (fibroblasts) migrate to mend wounds. But not all movement is desirable: Tumors are most dangerous when cancer cells gain the ability to travel throughout the body (metastasis). Certain bacteria and viruses can harness the cells' motility machinery to invade our bodies. Understanding how cells move--and the rod-like actin filaments that drive the process--is key to learning how to halt or promote motility to improve human health.

Now, using one of the most powerful microscopes in the world, scientists from Sanford Burnham Prebys Medical Discovery Institute (SBP) and University of North Carolina at Chapel Hill (UNC-Chapel Hill) have identified a dense, dynamic and disorganized actin filament nanoscaffold--resembling a haystack--that is induced in response to a molecular signal. This is the first time researchers have directly visualized, at the molecular level, a structure that is triggered in response to a cellular signal--a key finding that expands our understanding of how cells move. The study was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS).

"Cyro-electron microscopy is revolutionizing our understanding of the inner workings of cells," says Dorit Hanein, Ph.D., senior author of the paper and professor in the Bioinformatics and Structural Biology Program at SBP. "This technology allowed us to collect robust, 3D images of regions of cells--similar to MRI, which creates detailed images of our body. We were able to visualize cells in their natural state, which revealed a never-before-seen actin nano-architecture within the cell."

In the study, the scientists used SBP's cryo-electron microscope (Titan Krios), artificial intelligence (AI) and tailor-made computational and cell imaging approaches to compare nanoscale images of mouse fibroblasts to time-stamped light images of fluorescent Rac1, a protein that regulates cell movement, response to force or strain (mechanosensing) and pathogen invasion. This technically complex workflow--which bridged five orders of magnitude in scale (tens of microns to nanometers)--took years to develop to its current level of robustness and accuracy and was made possible through experimental and computational efforts of the structural biologist teams at SBP and the biosensors team at UNC-Chapel Hill.

The images revealed a densely packed, disorganized, scaffold-like structure comprised of short actin rods. These structures sprang into view in defined regions where Rac1 was activated, and quickly dissipated when Rac1 signaling stopped--in as little as two and a half minutes. This dynamic scaffold contrasted sharply with various other actin assemblies in areas of low Rac1 activation--some comprised of long, aligned rods of actin, and others comprised of short actin rods branching from the sides of longer actin filaments. The volume encasing the actin scaffold was devoid of common cellular structures, such as ribosomes, microtubules, vesicles and more, likely due to the structure's intense density.

"We were surprised that experiment after experiment revealed these unique hotspots of unaligned, densely packed actin rods in regions that correlated with Rac1 activation," says Niels Volkmann, Ph.D., a co-corresponding author of the paper who led the computational part of the study, and professor in the Bioinformatics and Structural Biology Program at SBP. "We believe this disorder is actually the scaffold's strength--it grants the flexibility and versatility to build larger, complex actin filament architectures in response to additional local spatial cues."

Next, the scientists would like to expand the protocol to visualize more structures that are created in response to other molecular signals and to further develop the technology to allow access to other regions of the cell.

"This study is only the beginning. Now that we developed this quantitative nanoscale workflow that correlates dynamic signaling behavior with the nano-scale resolution of electron cryo-tomography, we and additional scientists can implement this powerful analytical tool not only for deciphering the inner workings of cell movement but also for elucidating the dynamics of many other macromolecular machines in an unperturbed cellular environment," says Hanein.

She adds, "Actin is a building-block protein; it interacts with more than 150 actin binding proteins to generate diverse structures, each serving a unique function. We have a surplus of different signals that we would like to map, which could yield even more insights into how cells move."
-end-
Additional study authors include Daniel Marston, Ph.D.; Marie Rougie; and Klaus Hahn, Ph.D., of UNC-Chapel Hill; and Karen L. Anderson, Mark F. Swift and Christopher Page, Ph.D., of SBP. The study's DOI is 10.1073/pnas.1808830116.

Research reported in this press release was supported by the National Institutes of Health (NIH) (P01GM098412, R01GM115972, R01GM119948, P41EB002025, R35GM122596, S10OD012372 and P01GM098412S1) and the Leukemia & Lymphoma Society. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

About Sanford Burnham Prebys Medical Discovery Institute

Sanford Burnham Prebys Medical Discovery Institute (SBP) is an independent nonprofit medical research organization that conducts world-class, collaborative, biological research and translates its discoveries for the benefit of patients. SBP focuses its research on cancer, immunity, neurodegeneration, metabolic disorders and rare children's diseases. The Institute invests in talent, technology and partnerships to accelerate the translation of laboratory discoveries that will have the greatest impact on patients. Recognized for its NCI-designated Cancer Center and the Conrad Prebys Center for Chemical Genomics, SBP employs nearly 900 scientists and staff in San Diego (La Jolla), Calif. For more information, visit us at SBPdiscovery.org or on Facebook at facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.

Sanford Burnham Prebys Medical Discovery Institute

Related Actin Filaments Articles:

Terahertz radiation can disrupt proteins in living cells
Researchers from the RIKEN Center for Advanced Photonics and collaborators have discovered that terahertz radiation, contradicting conventional belief, can disrupt proteins in living cells without killing the cells.
Actin 'avalanches' may make memories stick
Avalanches in branched actomyosin networks are one possible mechanism by which the brain's neurons preserve memories.
Advance in understanding actin sheds light on cell function
A tiny chemical modification on one of the most abundant and important proteins in cells, actin, has long been somewhat mysterious, its function not fully understood, but scientists from the Perelman School of Medicine at the University of Pennsylvania have now taken a big step towards clearing up the mystery.
Simulations show fundamental interactions inside the cell
Actin filaments have several important functions inside cells. For one, they support the cell membrane by binding to it.
Actin filaments control the shape of the cell structure that divides plant cells
A Japanese research group using microscopic video analysis provides deeper insight into the mechanics of plant cell division.
Stop or go: The cell maintains its fine motility balance with the help of tropomodulin
Tropomodulin maintains the fine balance between the protein machineries responsible for cell movement and morphogenesis.
Physics of Life -- Lane change in the cytoskeleton
Many amphibians and fish are able to change their color in order to better adapt to their environment.
Lane change in the cytoskeleton
Many amphibians and fish are able to change their color in order to better adapt to their environment.
Revealing the structure of axons
Recent studies have shown that under the axonal membrane, rings composed of actin filaments give the structure its flexibility.
Cancer research: molecular machinery critical for cell's ability to move identified
Two specific proteins take apart the cell's actin filaments at one end and return the building blocks to the other end for a new round of polymerisation.
More Actin Filaments News and Actin Filaments Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#566 Is Your Gut Leaking?
This week we're busting the human gut wide open with Dr. Alessio Fasano from the Center for Celiac Research and Treatment at Massachusetts General Hospital. Join host Anika Hazra for our discussion separating fact from fiction on the controversial topic of leaky gut syndrome. We cover everything from what causes a leaky gut to interpreting the results of a gut microbiome test! Related links: Center for Celiac Research and Treatment website and their YouTube channel
Now Playing: Radiolab

The Flag and the Fury
How do you actually make change in the world? For 126 years, Mississippi has had the Confederate battle flag on their state flag, and they were the last state in the nation where that emblem remained "officially" flying.  A few days ago, that flag came down. A few days before that, it coming down would have seemed impossible. We dive into the story behind this de-flagging: a journey involving a clash of histories, designs, families, and even cheerleading. This show is a collaboration with OSM Audio. Kiese Laymon's memoir Heavy is here. And the Hospitality Flag webpage is here.