Applied physicists discover that migrating cells flow like glass

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The research, led by investigators at Harvard's School of Engineering and Applied Sciences (SEAS) and the University of Florida, advances scientists' understanding ofwound healing,cancer metastasis, and embryonic development.

The finding was published online February 14 inProceedings of the National Academy of Sciences.

Cellsoften move from one part of the body to another. In a developing embryo, for example, cells in the three germ layers have to arrange themselves spatially so that the cells that will become skin are all on the outside. Similarly, as acancerous tumorexpands, the cells proliferate and push others aside. In wound healing, too, new cells have to move in to replace damaged tissue.

It is well known that cells accomplish these movements through internal cytoskeletal rearrangements that allow them to extend, retract, and divide. At some point during the migration, though, the new tissue settles into place and stops.

"We're trying to understand it from a fundamental point of view,"says principal investigator David Weitz, Mallinckrodt Professor of Physics and Applied Physics at SEAS."What we're really trying to get at is, why do things stop moving?"

The glass under discussion here is not the kind used in windows—though that is part of the larger category. Glasses include any amorphous materials that are viscous enough to remain solid for a reasonable period of time (often considered to be 24 hours) but which flow over longer periods (see sidebar).

Cream that is churned into butter goes through a sort of glass transition, as the increasing density of particles in the fatty emulsion forces it to become solid. Like any glass, butter will lose its form if the temperature rises.

As supercooled fluids and colloids (like cream) become more dense and approach the glass transition, the particles exhibit certain characteristic motions.

"We study this extensively,"says Weitz, who leads the Experimental Soft Condensed Matter Group at SEAS."We take small particles, and we increase their concentration more and more until they stop moving and they become a glass—and we understand how that behaves very well."

Living cells, though, add several levels of complexity to the system: they vary in size, shape, and rigidity; they divide; they sense their environment; and they exert their own forces on their surroundings.

"What is really surprising to us in this research with tissues,"says Weitz,"is that many of the features that inert particles exhibit as their concentration increases are also exhibited by cells. The real qualitative difference is that small particles move only because of thermal motion, whereas cells actually move themselves."

This is an artist's representation of epithelial cells (black) approaching the glass transition (blue). Increasingly large groups of cells (green, purple, red) are able to move together more rapidly than the surrounding cells. Credit: Image courtesy of Thomas E. Angelini, University of Florida.

To simulate and study the migration of living tissue, Weitz's team deposited thousands of epithelial cells—specifically, canine kidney cells—onto a polyacrylamide gel containing the protein collagen. The researchers watched them grow and move under a microscope while measuring the individual and collective cellular movements, as well as the changes in density caused by proliferation.

The researchers found that when the cells are in a confluent layer (meaning that the cells are close enough to be touching), they flow like a liquid. However, when cell density increases past a certain threshold, the tightly packed cells begin to inhibit each other's movement. As a result, some cells are able to travel in groups, while others hardly get to move at all.

In other words, they behave just like a supercooled fluid or colloidal suspension transitioning into a glass.

"The implications for biological processes are very surprising,"says lead author Thomas E. Angelini, formerly a postdoctoral researcher at SEAS and now an Assistant Professor at the University of Florida.

"Imagine a model wound in which a large group of cells are removed from the middle of a confluent layer,"he says."Cells will migrate inward to fill the void. Our results demonstrate that the low density of cells in the center of the wound is analogous to a raised temperature in the center of a molecular glass, causing flow within the hotter region."

"You could say that a wound is melted glass."

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Gas rich galaxies confirm prediction of modified gravity theory

Modern cosmology says that for the universe to behave as it does, the mass-energy of the universe must be dominated bydark matteranddark energy. However, direct evidence for the existence of these invisible components remains lacking. An alternate, though unpopular, possibility is that the currenttheory of gravitydoes not suffice to describe the dynamics of cosmic systems.

A few theories that would modify our understanding of gravity have been proposed. One of these is Modified Newtonian Dynamics (MOND), which was hypothesized in 1983 by Moti Milgrom a physicist at the Weizmann Institute of Science in Rehovot, Israel. One of MOND's predictions specifies the relative relationship between the mass of any galaxy and its flat rotation velocity. However, uncertainties in the estimates of masses of stars in star-dominated spiral galaxies (such as our own Milky Way) previously had precluded a definitive test.

To avoid this problem, McGaugh examined gas rich galaxies, which have relatively fewer stars and a preponderance of mass in the form ofinterstellar gas."We understand the physics of the absorption and release of energy by atoms in the interstellar gas, such that counting photons is LIKE counting atoms. This gives us an accurate estimate of the mass of such galaxies,"McGaugh said.

Using recently published work that he and other scientists had done to determine both the mass and flat rotation velocity of many gas rich galaxies, McGaugh compiled a sample of 47 of these and compared each galaxy's mass AND rotation velocity with the relationship expected by MOND. All 47 galaxies fell on or very close to the MOND prediction. No dark matter model performed as well.

"I find it remarkable that the prediction made by Milgrom over a quarter century ago performs so well in matching these findings for gas rich galaxies,"McGaugh said."

MOND vs. Dark Matter - Dark Energy

Almost everyone agrees that on scales of large galaxy clusters and up, the Universe is well described by dark matter - dark energy theory. However, according to McGaugh this cosmology does not account well for what happens at the scales of galaxies and smaller.

"MOND is just the opposite,"he said."It accounts well for the 'small' scale of individual galaxies, but MOND doesn't tell you much about the larger universe.

Of course, McGaugh said, one can start from the assumption of dark matter and adjust its models for smaller scales until it fits the current finding."This is not as impressive as making a prediction ahead of {new findings}, especially since we can't see dark matter. We can make any adjustment we need."This is rather like fitting planetary orbits with epicycles,"he said. Epicycles were erroneously used by the ancient Greek scientist Ptolemy to explain observed planetary motions within the context of a theory for the universe that placed the earth in its center.

"If we're right about dark matter, why does MOND work at all?"asks McGaugh."Ultimately, the correct theory - be it dark matter or a modification of gravity - needs to explain this."

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Large Hadron Collider powers up to unravel mysteries of nature

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On Monday, theCERNControl Center turned on the LHC beams to begin the next two-year run of the particle collider. CERN directors decided to extend the run through the end of 2012, instead of shutting down in 2011 for repairs as previously planned, and spirits are running high among scientists working in the field of new physics.

Researchers from across the world engineer detectors and seek to solve the mysteries of matter in an international collaboration that reaches from Chicago to Mumbai.

“Recently there was a convention in Chamonix,” said Georgios Choudalakis, a Greek physicist on the ATLAS experiment at the LHC.“The heads of the experiments and the director of the laboratory decided that we will take data for 2 years. And the decisive criterion for this was the sensitivity to the Higgs, so we’re optimistic.”

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The search is on for the Higgs! The international team of scientists at CERN recalls the bumpy history of the Large Hadron Collider, from disastrous delays to recent results that are exceeding expectations. The physicists anticipate breakthroughs in the next two years that will change our fundamental understanding of the universe. Video credit: Chelsea Whyte and Justin Eure/MEDILL.

This comes on the heels of the news that 2011 will be the end of the run for the Tevatron, the second most powerful particle collider in the world located at the Fermi National Laboratory in Batavia. After setbacks and shutdowns, the LHC had collisions in 2010 that went even better than expected.“We made it clear even to ourselves that the page has turned,” said Choudalakis.“The energy frontier is not at the Tevatron anymore. We are cutting more ice here.”

Now, the hunt for the Higgs is on at CERN, the Conseil Européen pour la Recherche Nucléaire.

The elusive Higgs particle is, according to the theory, a fundamental building block of matter and the reason everything has mass.

“Nobody can explain where mass comes from, but we know it’s there,” said Pauline Gagnon, a French physicist at theATLAS experiment. This conundrum is the most important question physicists have to answer, she said.

“If you think of a one pound bag of salt and you add up the weights of each grain of salt, they will logically equal one pound,” said Gagnon. But, when physicists break down atoms in this way and try to determine the weight of the pieces inside, the calculations of the weight of atomic building blocks such as quarks and electrons don’t add up, she said. Here’s where the Higgs comes in.

The proposed Higgs particle is a part of a field that permeates everything. According to theory, it is a particle’s interaction with the Higgs field that creates drag on a particle, giving it mass. Picture a business man walking through a pool in a suit. The water in the pool is like the Higgs field and, as it soaks into his clothing, it will weigh him down and he will move more slowly. He becomes massive.

Although it has been predicted as the final puzzle piece that completes the Standard Model of physics– the leading explanation for atomic interaction– the existence of the Higgs has never been proven. If such a particle exists, experiments at the LHC should be able to detect it.

“We have indirect suggestions of where it should be if the Higgs exists,” said Choudalakis.“But that is if it exists.” If it can’t be found, the Standard Model will have to be rewritten.

In the next two years, the LHC will resume collisions at 7 TeV, or tera electron volts, between the two beams– the highest energy levels achieved in recent years. The decision at Chamonix mandates that energy in the beams will be kept at this conservative level to avoid the types of machine failures that shut down the LHC in 2008, Gagnon said.

At those energy levels, the two particle beams travel through miles of tubes surrounded by 1,700 superconducting magnets that force bunches of charged particles around the ring and through accelerators designed to increase their speed to within a percentage of the speed of light.

The particle beams, each made up of hundreds of billions of protons, began making their way around a series of underground tubes Monday, guided magnetically and gaining speed and energy. The beams start out about as big around as an index finger and, within microseconds they complete their journey through the four accelerator rings into the LHC and are compressed down to the size of a human hair.

“The beams, at 7 TeV, will have an energy which is the same kinetic energy of a 747 landing, so imagine a big airplane which is landing and smashing against a wall– this is the energy of the LHC beams,” said Mirko Pojer, an Italian and the engineer in charge of the CERN Control Center.

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The sections of beam tube that make up the main ring of the LHC are surrounded superconducting magnets that each weigh 27 tons. Credit: Justin Eure/MEDILL

The two beams, moving in opposite directions, collide at 4 points along the ring where the separate LHC experiments house their detectors, which gather data to analyze the collisions that occur every 25 nanoseconds.

Two of the experiments at CERN are designed to detect a possible Higgs particle. Though they have the same goal, the ATLAS and CMS detectors are designed to look at particle collisions differently.

ATLAS, the larger of the two detectors, stands 82 feet high and houses an enormous magnet system that bends the paths of charged particles after collisions in order to measure their momentum, which identifies them.

CMS, the Compact Muon Solenoid, as its name suggests, is more compact than ATLAS. The CMS detector is designed around a large coiled magnet, which creates a uniform magnetic field that is 100,000 stronger than the Earth’s. CMS measures the subatomic debris of the collisions, hunting for signs of the Higgs.

The 3,000 scientists at ATLAS and the 2,000 scientists at CMS are in a race to be the first to make the biggest scientific discovery of the century.

The next two years of operation will provide enough particle collisions for a groundbreaking discovery. If the Higgs exists, the physicists at CMS or ATLAS will see evidence of the particle. With the amount of data that the LHC will be able to gather in the next two years, scientists expect to confirm the existence or absence of the Higgs, said Gigi Rolandi, an Italian and the physics coordinator for the CMS.

These detectors are truly wonders of the modern age. Like the Acropolis or the Great Wall of China, the LHC is just as incredible a feat of engineering, though it cannot be seen as readily.“It’s a real pity that these detectors are underground,” said Choudalakis.“If they were on the surface, everybody would be very proud of what mankind has done.”

At CERN, the discovery of the fundamental building blocks of nature are just around the corner.“People are thrilled by this, and well deservedly,” said Choudalakis.“What is beautiful about science, especially on a big scale like this, is that it makes you feel like you have a little chance in your life, from your humble starting point, to touch your finger on history and leave a fingerprint on it. Imagine history as a big piece of glass. Most people don’t even get close, and you have a chance to leave your fingerprint on it. I think it’s one of the noblest missions a person can have.”

While the discovery of the Higgs would indeed be a milestone for the world of physics, and a tidy completion of the Standard Model, sometimes messy is far more interesting.

“Like we say, if we do not discover the Higgs particle, it will be even more interesting to find out what else is there in the physics and in nature which then controls the amplitudes of interactions of the particles,” said Slawomir Tkaczyk, a Polish physicist on the CMS experiment.“So, after 10 or 15 years of hard work, the most exciting times are still ahead of us.”

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This story is republished courtesy of Medill Reports.Medill Reportsis written and produced by graduate journalism students at Northwestern University's Medill school.

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Outside the small village of Meyrin, Switzerland, horses graze quietly in fields lined by the Jura mountains. You'd never know it by the idyllic landscape, but 300 feet below the Swiss-French border, the Large ...

Physics/General Physics

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Small particle means big research for international physics project

They're looking atneutrinos,tiny particleswith a major influence on physics research.

Glenn Horton-Smith, associate professor of physics, is leading the K-State exploration on the Double Chooz neutrino detector, located in the Ardennes region of northern France. The detector measures neutrinos from the nearby Chooznuclear power plant.

More than 38 universities and research institutes from eight countries are working on the neutrino detector. K-State is one of 14 U.S. organizations involved.

Neutrinos are neutralelementary particlesthat come from nuclear reactions orradioactive decay, and large detectors are needed to capture and measure them.

The detector is buried more than 300 feet inside a hill a little more than a half of a mile away from the nuclear reactor and is the site of a previous neutrino experiment. Construction on the first of two new neutrino detectors finished in late 2010.

"It's exciting because we're in a data-taking stage right now,"Horton-Smith said."We're looking at the first data that is coming out and making sure everything is working correctly."

K-State scientists, along with K-State's Electronics Design Lab, designed and built the hardware for the detector's monitoring system, which measures the magnetic field and temperature throughout the detector. Horton-Smith wrote the first computer simulation of the detector, and he leads the group of researchers who work on offline data processing and simulation software.

The hardware and software help the detector measure neutrino oscillations, which are the transformations of neutrinos into different types. Neutrinos come in three different types, each an overlapping of three different mass states. As these states oscillate, a neutrino's type changes.

"It is very analogous to a musical chord, where you hear two or three frequencies at the same time,"Horton-Smith said.

While two mass states have been detected in the neutrinos from reactors, the third state is either weak or absent. Researchers in the Double Chooz collaboration want to discover more about this third mass state.

To capture and measure neutrinos, the detector includes a central cylinder 10.5 cubic meters in size that is surrounded by larger cylinders. The cylinders are filled with a clear liquid scintillating oil that glows when neutrinos interact and measures energy deposited by radiation and subatomic particles. Several layers of buffer liquid and steel act as protection.

"We're really checking to see whether all three mass states are in the electron neutrino, or if one of them is missing,"Horton-Smith said."If one of them is missing, there are all sorts of theories about why that may be."

Researchers will collect data throughout the year from the first detector. The second detector, scheduled to be completed in 2012, will be even closer to thenuclear reactor-- more than 1,300 feet. By comparing data from both detectors at two different distances, researchers hope to have more accurate measurements of neutrino oscillations.

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'Fingerprints' match molecular simulations with reality

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ORNL's Jeremy Smith collaborated on devising a method -- dynamical fingerprints -- that reconciles the different signals between experiments andcomputer simulationsto strengthen analyses of molecules in motion. The research will be published in theProceedings of the National Academy of Sciences.

"Experiments tend to produce relatively simple and smooth-looking signals, as they only 'see' a molecule's motions at low resolution,"said Smith, who directs ORNL's Center forMolecular Biophysicsand holds a Governor's Chair at the University of Tennessee."In contrast, data from a supercomputer simulation are complex and difficult to analyze, as the atoms move around in the simulation in a multitude of jumps, wiggles and jiggles. How to reconcile these different views of the same phenomenon has been a long-standing problem."

The new method solves the problem by calculating peaks within the simulated and experimental data, creating distinct"dynamical fingerprints."The technique, conceived by Smith's former graduate student Frank Noe, now at the Free University of Berlin, can then link the two datasets.

Supercomputer simulations and modeling capabilities can add a layer of complexity missing from many types of molecular experiments.

"When we started the research, we had hoped to find a way to use computer simulation to tell us which molecular motions the experiment actually sees,"Smith said."When we were finished we got much more -- a method that could also tell us which other experiments should be done to see all the other motions present in the simulation. This method should allow major facilities like the ORNL's Spallation Neutron Source to be used more efficiently."

Combining the power of simulations and experiments will help researchers tackle scientific challenges in areas like biofuels, drug development, materials design and fundamental biological processes, which require a thorough understanding of how molecules move and interact.

"Many important things in science depend on atoms and molecules moving,"Smith said."We want to create movies of molecules in motion and check experimentally if these motions are actually happening."

View asupercomputer simulationof a protein in motion here: http://www.ornl.gov/ornlhome/hg_mer.htm

"The aim is to seamlessly integrate supercomputing with the Spallation Neutron Source so as to make full use of the major facilities we have here at ORNL for bioenergy and materials science development,"Smith said.

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