Uncovering the secrets of cellular organization

A 3D hydrogel model provides key insights into how cells sense respond to elements of their environments.

Our cells constantly perform a carefully choreographed dance, arranging themselves into complex tissues. Some cues directing this cellular ballet are known, such as chemical electrical gradients for example. There now appears to be a more universal set of cues instructing cells: the physical parameters of the environment itself.

Since the invention of agar Petri dishes in the late 19th century, cells have been studied on flat, stiff surfaces, which hardly resemble their natural environment. More recently, cell behavior has been studied in dispersed 3D gels, but never in curved or folded environments.

Now, due to advances in fabrication techniques of soft gelatin hydrogels, a team from John’s Hopkins University, the University of Maryland, the John’s Hopkins School of Medicine can create specific microscale 3D settings that amount to cell-sized mountains valleys in which they can observe cellular behavior. In their paper published in Advanced Science, they showed that cells do in fact sense respond to physical aspects of their surroundings.

“We have discovered that cells can organize by measuring something,” said David Gracias, professor in chemical biomolecular engineering at John’s Hopkins University one of the authors of the paper. “It’s kind of like a cellular ruler.”

A guiding hydrogel

What they measured is the stiffness aspect ratio of wells printed into the hydrogel — aspect ratio being the ratio of the well’s perimeter to its depth stiffness measured in kilopascal (kPa), a unit describing a material’s resistance to being deformed.

The team observed that cells in softer 2 kPa wells were 30 times more likely to organize in a ringed pattern around the edge of the well compared to cells in stiffer 35 kPa wells, which spread out evenly across the well. Furthermore, this behavior was strongly correlated to the well’s aspect ratio. Increase or decrease the ratio too much, the cells stopped forming the rings.

Confocal images showing stained cells 24h after seeding in hydrogel microwells

Importantly, these hydrogels don’t contain chemical signals. “There are no micro patterns or gradients of chemical stimuli that are also affecting the cell behavior,” said co-author Lewis Romer, a physician professor of anesthesiology critical care medicine at the John’s Hopkins School of Medicine. “The ligands for cell attachment are homogenously available across the surface.”

This uniform biochemical environment means the cells must be sensing the aspect ratio stiffness of their environment using these cues alone to organize. In a fun demonstration of the specificity of this response, the team placed cells on a hydrogel imprinted with letters at the right stiffness aspect ratio watched as they formed the word CELL.

An unexplored signalling pathway

It’s easy to see tissue engineering applications, such as the production of organoids — small organ-like structures used for research. But there are more fundamental implications for this work too. Sensing these cues means the cells are using some still undescribed signalling pathway, something the team is eagerly hoping to map out in the future.

The body is also a dynamic 3D environment in which aspect ratio stiffness change over time. Exactly how cells respond to these parameters might explain how critically important tissues, like the vascular system, develop respond to aging disease. “To think that, that process of vascular network formation may be extremely responsive to aspect ratio would help us to guide the kinds of questions we want to ask in a developmental biology context,” said Romer.

Romer’s research also focuses on a group of vascular diseases called pulmonary hypertension. “One of the themes in the development of that kind of vascular disease others as well, corona artery disease, arterial sclerosis, is this issue of stiffness.”

These diseases, even aging itself, come with the stiffening of vascular tissues, says Romer, the discovery of the importance of stiffness aspect ratio to cellular organization provides intriguing avenues of inquiry targets for treatment. “It’s a specific kind of target, specific new signalling frontier that can be interrogated.”  

Reference: Gayatri J. Pahapale, et al., Directing Multicellular Organization by Varying the Aspect Ratio of Soft Hydrogel Microwells, Advanced Science (2022). DOI: 10.1002/advs.202104649

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Extreme ‘Black Widow’ Pulsar Detected Just 3,000 Light-Years Away

There are some strange objects lurking in our galaxy, astronomers have just spied an extreme new candidate roughly 3,000 to 4,000 light-years away. 

After investigating mysterious flashes of light coming from the system, researchers have detected what they suspect is an elusive ‘black widow’ star – a rapidly spinning pulsar that’s kept alive by slowly devouring its smaller companion star.


Black widow pulsars are rare at best – we only know of a dozen or more of them in the Milky Way. But this one appears to be among the most extreme, arguably most bizarre, examples of the phenomenon we’ve ever found. 

Named ZTF J1406+1222, the binary system has the shortest orbital period yet seen, with the ‘black widow’ its prey circling each other every 62 minutes. 

Even more peculiar, the system seems to host a third, far-flung star that takes roughly 12,000 years to orbit the other two.

“This system is really unique as far as black widows go, because we found it with visible light, because of its wide companion, the fact it came from the galactic center,” says lead researcher physicist Kevin Burdge from MIT’s Department of Physics. 

Pulsars arise when the cores of massive supergiant stars collapse into neutron stars. When these neutron stars are highly magnetized rapidly spinning, they become what we call a pulsar. 

Like ultra-bright lighthouses in the Universe, pulsars spin around extremely rapidly shine X-rays gamma rays towards us at intervals ranging from more than one a second, down to periods that can be counted in milliseconds. Normally pulsars spin fast die young, due to how much energy they’re blasting out. 


But if a passing star gets close enough, the pulsar can slowly suck material from it like a giant parasite, siphoning enough energy to continue spinning feeding off the other star until it devours it.

“These systems are called black widows because of how the pulsar sort of consumes the thing that recycled it, just as the spider eats its mate,” says Burdge.

In the past, astronomers have been alerted to these black widow systems through gamma rays or X-rays – high frequency radiation blasted out by the pulsar itself.

But the team used a new technique to find ZTF J1406+1222: they looked for visible light coming off the star being eaten.

It turns out the ‘day’ side of the companion star that’s locked with the black widow can get many times hotter than the ‘night’ side, this extreme variation in brightness is something that can be detected. 

To test this idea, the researchers used data from Zwicky Transient Facility, an observatory in California, were able to find the black widow systems we already know about, validating that the technique worked. 


They then set about looking for new black widows, came across ZTF J1406+1222, where the companion star changes in brightness by a factor of 13 every 62 minutes.

This is the first time a black widow pulsar has been found this way, that’s part of what makes the discovery so exciting.

 (NASA Goddard Space Flight Center/Cruz deWilde)

Above: The black widow’s gamma-rays (magenta) heat the fiery ‘day’ side of the star.

The other part, of course, is the mysterious system they stumbled upon.

Not only are the black widow pulsar its prey locked in the tightest cannibalistic spiral seen to date, but when the team looked back through measurements of the star using the Sloan Digital Sky Survey, they saw the system was being trailed by a rare low-metallicity cool subdwarf star, which appeared to only orbit the binary every 12,000 years.

The presence of this far-flung third star could make the system an unheard-of ‘triple’ black widow, has astronomers scratching their heads about how the set-up could have formed in the first place.


Based on current observations, Burdge his colleagues have a few ideas. Black widow binaries arise from a dense constellation of old stars known as a globular cluster.

One of the leading hypotheses is that, if this particular cluster drifted into the center of the Milky Way, then the gravity of our central black hole may have pulled the cluster apart while sparing only the triple black widow.

“It’s a complicated birth scenario,” says Burdge. “This system has probably been floating around in the Milky Way for longer than the Sun has been around.”

Even weirder, while the team could detect ZTF J1406+1222 using visible light, when they looked back for gamma X-rays, they couldn’t actually see it – which suggests that it actually may not be a black widow at all.

“The one thing we know for sure is that we see a star with a day side that’s much hotter than the night side, orbiting around something every 62 minutes,” says Burdge.

“Everything seems to point to it being a black widow binary. But there are a few weird things about it, so it’s possible it’s something entirely new.”

The team plans to continue observing the system to get a better idea of what’s going on.

Intriguingly, it could be a prime candidate for learning more about neutron star ‘kick’ physics. Astronomers know that when neutron stars form they get a ‘kick’ that sends them speeding off at a high velocity.

But it’s not fully understood where this kick comes from. The strange birth story of this mysterious system could shed light on the question.

“There’s still a lot we don’t understabout it. But we have a new way of looking for these systems in the sky.”

The research has been published inNature. 


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Huge Solar Flare Bursting From The Sun Is Second of Its Kind This Week, NASA Says

A powerful solar flare just erupted from the surface of the Sun – NASA captured stunning footage of it.

The X-class flare, the strongest produced by our star, was recorded by NASA’s Solar Dynamics Observatory as it burst from a sunspot on the lower left limb of the Sun at 9:25 am EDT (13:25 GMT) on Tuesday (May 3).


Sunspots are areas on the Sun’s surface where powerful magnetic fields, created by the flow of electrical charges, knot into kinks before suddenly snapping. The resulting release of energy launches bursts of radiation called solar flares explosive jets of solar material called coronal mass ejections (CMEs).

Related: Strange new type of solar wave defies physics

The National Oceanic Atmospheric Administration (NOAA) classifies solar flares from A to X based on the intensity of the X-rays they release, with each level having 10 times the intensity of the last.

This flare registered as an X1.1, is the second flare of this strength to be produced by the Sun this week. It’s also the third most powerful solar flare of 2022: The star launched an X2.2 flare on April 19 an X1.3 on March 30.


“Solar flares are powerful bursts of radiation,” NASA wrote on Twitter after the event.

“Harmful radiation from a flare cannot pass through Earth’s atmosphere to physically affect humans on the ground, however – when intense enough – they can disturb the atmosphere in the layer where GPS communications signals travel.”

Once they reach Earth, X-rays ultraviolet radiation produced by solar flares ionize atoms in our upper atmosphere, making it impossible to bounce high-frequency radio waves from them creating a radio blackout.

Radio blackouts occur over the areas lit by the Sun during the time of the flare, they are classified from R1 to R5 according to severity.

This most recent flare caused an R3 blackout over the Atlantic Ocean, which is the same strength as the flare-induced blackout over Australia Asia during Easter weekend last month.

Solar activity, which astronomers have known since 1775 rises falls according to a roughly 11-year cycle, has been especially high recently, with sunspot counts nearly doubling those predicted by NOAA.

The increased activity has sent waves of high-energy plasma X-ray bursts slamming into Earth’s magnetic fields, downing Starlink satellites, triggering radio blackouts causing auroras as far south as Pennsylvania, Iowa, Oregon.


And the most intense activity may still lie ahead. The Sun’s activity is projected to steadily climb, reaching an overall maximum in 2025, before decreasing again.

This ramp-up in activity means that, on the night of a solar storm, the aurora will be visible much farther south than usual.

This is because Earth’s magnetic field gets compressed slightly by the waves of highly energetic particles, which ripple down magnetic field lines agitate molecules in the atmosphere, releasing energy in the form of light to create colorful shifting curtains in the night sky.

Related content:

15 unforgettable images of stars

The 12 strangest objects in the Universe

9 ideas about black holes that will blow your mind

This article was originally published by Live Science. Read the original article here.


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There Are Mountains of Sugar Hidden in The Ocean, And We’ve Only Just Found Out

Hidden below the waves, the ocean contains vast reserves of sugar that we never were aware of, according to new research.

Scientists have discovered that seagrass meadows on the ocean floor can store huge amounts of the sweet stuff underneath their waving fronds – there are major implications for carbon storage climate change.


The sugar comes in the form of sucrose (the main ingredient of sugar used in the kitchen), it’s released from the seagrasses into the soil underneath, an area directly affected by the roots, known as the rhizo­sphere. It means seabed sugar concentrations are some 80 times higher than they would be normally.

Worldwide, seagrasses could be sitting on up to 1.3 million tons of sucrose, the research team says. To put it another way, that’s enough for about 32 billion cans of Coca-Cola, so we’re talking about a substantial find of hidden sugar.

“Seagrasses pro­duce sugar dur­ing photosynthesis,” says marine microbiologist Nicole Dubilier from the Max Planck Institute for Marine Microbiology in Germany.

“Un­der average light conditions, these plants use most of the sug­ars they pro­duce for their own meta­bol­ism growth. But un­der high light con­di­tions, for ex­ample at mid­day or dur­ing the sum­mer, the plants pro­duce more sugar than they can use or store. Then they re­lease the excess sucrose into their rhizosphere. Think of it as an over­flow valve.”


What’s surprising is that this excess sugar isn’t gobbled up by microorganisms in the surrounding environment. To stop this, it seems seagrasses send out phenolic compounds in the same way as many other plants do.

These chemical compounds – found in red wine, coffee, fruit, as well as many other places in nature – are antimicrobials that inhibit the metabolism of most microorganisms, slowing them down.

The researchers tested out their hypothesis in an actual underwater seagrass field to confirm that this is indeed what was happening, via a mass spectrometry technique.

Studying seagrasses on the seafloor. (HYDRA Marine Sciences GmbH)

“In our ex­per­i­ments we ad­ded phen­olics isol­ated from seagrass to the mi­croor­gan­isms in the seagrass rhizo­sphere,” says marine microbiologist Maggie Sogin from the Max Planck Institute for Marine Microbiology.

“And in­deed, much less sucrose was con­sumed com­pared to when no phenolics were present.”

A small set of microbes actually thrived on the sucrose despite the presence of phenolics: the researchers think that these “microbial specialists” are perhaps giving something back to the seagrass in return, like nutrients they need to grow.


Seagrasses are some of the planet’s most important sinks for blue carbon (carbon captured by the world’s ocean coastal ecosystems): an area of seagrass can suck up twice as much carbon as a forest of the same size on land, 35 times as fast too.

When it comes to calculating carbon capture loss from the seagrass meadows – among the most threatened habitats on the planet due to human activity decreasing water quality – scientists can now factor in the sucrose deposits as well as the seagrass itself.

“We do not know as much about seagrass as we do about land-based hab­it­ats,” says So­gin.

“Our study con­trib­utes to our un­der­stand­ing of one of the most crit­ical coastal hab­it­ats on our planet, high­lights how im­port­ant it is to pre­serve these blue car­bon eco­sys­tems.”

The research has been published in Nature Eco­logy & Evol­u­tion.


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Incredible Footage Shows Drone Swarm Navigate Thick Forest With Eerie Precision

A swarm of 10 bright blue drones lifts off in a bamboo forest in China, then swerves its way between cluttered branches, bushes, over uneven ground as it autonomously navigates the best flight path through the woods.


The experiment, led by scientists at Zhejiang University, evokes scenes from science fiction – the authors in fact cite films such as Star Wars, Prometheus, Blade Runner 2049 in the opening of their paper published Wednesday in the journal Science Robotics.

“Here, we take a step forward (to) such a future,” wrote the team, led by Xin Zhou.

In theory, there are myriad real-world applications, including aerial mapping for conservation disaster relief work. But the technology has needed to mature so that flying robots can adapt to new environments without crashing into one another or objects, thus endangering public safety.

Drone swarms have been tested in the past, but either in open environments without obstacles, or with the location of those obstacles programmed in, Enrica Soria, a roboticist at the Swiss Federal Institute of Technology Lausanne, who was not involved in the research, told AFP.

“This is the first time there’s a swarm of drones successfully flying outside in an unstructured environment, in the wild,” she said, adding the experiment was “impressive”.

The palm-sized robots were purpose-built, with depth cameras, altitude sensors, an on-board computer. The biggest advance was a clever algorithm that incorporates collision avoidance, flight efficiency, coordination within the swarm.


Since these drones do not rely on any outside infrastructure, such as GPS, swarms could be used during natural disasters.

For example, they could be sent into earthquake-hit areas to survey damage identify where to send help, or into buildings where it’s unsafe to send people.

It’s certainly possible to use single drones in such scenarios, but a swarm approach would be far more efficient, especially given limited flight times.

Another possible use is having the swarm collectively lift deliver heavy objects.

There’s also a darker side: swarms could be weaponized by militaries, just as remote-piloted single drones are today. The Pentagon has repeatedly expressed interest is carrying out its own tests.

“Military research is not shared with the rest of the world just openly, so it’s difficult to imagine at what stage they are with their development,” said Soria.

But advances shared in scientific journals could certainly be put to military use.

Coming soon?

The Chinese team tested their drones in different scenarios – swarming through the bamboo forest, avoiding other drones in a high-traffic experiment, having the robots follow a person’s lead.

“Our work was inspired by birds that fly smoothly in a free swarm through even very dense woods,” wrote Zhou in a blog post.


The challenge, he said, was balancing competing demands: the need for small, lightweight machines, but with high-computational power, plotting safe trajectories without greatly prolonging flight time.

For Soria, it’s only a matter of a few years before we see such drones deployed in real-life work. First, though, they will need to be tested in ultra-dynamic environments like cities, where they’ll constantly come up against people vehicles.

Regulations will also need to catch up, which takes additional time.​

© Agence France-Presse


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