Cell biologists at Johns Hopkins have identified key steps in how certain molecules alter a cell’s skeletal shape and drive the cell’s movement.
Results of their research, published in the December 13 issue of Science Signaling, have implications for figuring out what triggers the metastatic spread of cancer cells and wound-healing.
“Essentially we are figuring out how cells crawl,” says Takanari Inoue, Ph.D., an assistant professor of cell biology and member of the Center for Cell Dynamics in the Johns Hopkins University School of Medicine’s Institute for Basic Biomedical Sciences. “With work like ours, scientists can reveal what happens when cells move when they aren’t supposed to.”
Their new discovery highlights the role of the cell’s skeleton, or cytoskeleton, in situations where “shape shifting” can rapidly change a cell’s motion and function in response to differing environmental conditions.
When cell’s such as fibroblasts, which gather to heal wounds, move from one place to another, its cytoskeleton forms ripple-like waves or ruffles across its surface that move towards the front of the cell and down, helping pull the cell across a surface. Researchers have shown that these ruffles form when a small molecule, PIP2, appears on the inside surface of the membrane at the front edge of a cell. Until now, however, they have been unable to recreate cell ruffles simply by directing PIP2 to the cell’s front edge. Manipulations have instead led the cytoskeleton to form completely different structures, squiggles that zip across the inside of the cell like shooting stars across the sky, which the researchers call comets.
In their experiments, Inoue and his group looked for factors that determined whether a cell forms ruffles or comets. The researchers tried to create ruffles on the cell by sending in an enzyme to the cell membrane that converts another small molecule into PIP2. Using cytoskeleton building blocks marked to glow, the team used a microscope to watch the cytoskeleton assembling itself and saw that this approach caused the cytoskeleton to form comets, not the ruffles that the researchers had predicted.
The team suspected that comets formed because of a fall in levels of another small molecule used to make PIP2, PI4P.
To test this idea, the researchers tried to make ruffles on cells only by increasing PIP2 at the membrane, rather than changing the quantities of any other molecules. Using molecular tricks that hid existing PIP2 then revealed it, the researchers effectively increased the amount of available PIP2 at the membrane. This time the researchers saw ruffles.“Now that we’ve figured out this part of how cells make ruffles, we hope to continue teasing apart the mechanism of cell movement to someday understand metastasis,” says Inoue.
“It will be interesting to manipulate other molecules at the cell surface to see what other types of cytoskeletal conformations we can control,” he says.
Tasuku Ueno and Christopher Pohlmeyer of Johns Hopkins University School of Medicine and Björn Falkenburger of the University of Washington were additional authors of the study.
This study was funded by grants from the National Institutes of Health and the Japan Society for the Promotion of Science.
*Images available upon request*Videos:
_light_to_move_moleculesResearchers Put Proteins Right Where They Want Them: Location Determines a Protein's Role: http://www.hopkinsmedicine.org/news/media/releases/Hopkins_Researchers_Put
_Proteins_Right_Where_They_Want_ThemTakanari Inoue on the leading edge of migrating cells: http://www.hopkinsmedicine.org/institute_basic_biomedical_sciences/about_us
/scientists/takanari_inoue.htmlOn the Web:
Institute for Basic Biomedical Sciences: http://www.hopkinsmedicine.org/institute_basic_biomedical_sciences/
Vanessa McMains | Newswise Science News
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy