Strange and complex behavior of frog cell blobs

A xenobot “parent,” shaped like a hungry Pac-Man (shown in red false color), created an “offspring” xenobot (green sphere) by gathering loose frog cells in its opening.

Tiny “living machines” made of frog cells can make copies of themselves. This newly discovered renewal mechanism may help create self-renewing biological machines.

According to Kirstin Petersen, an electrical and computer engineer at Cornell University who studies groups of robots, “this is an extremely exciting breakthrough.” She says self-replicating robots are a big step toward human-free systems.

Researchers described the behavior of xenobots earlier this year (SN: 3/31/21). Small clumps of skin stem cells from frog embryos knitted themselves into small spheres and started moving. Cilia, or cellular extensions, powered the xenobots around their lab dishes.

The findings are published in the Proceedings of the National Academy of Sciences on Dec. 7. The xenobots can gather loose frog cells into spheres, which then form xenobots.
The researchers call this type of movement-induced reproduction kinematic self-replication. The study's coauthor, Douglas Blackiston of Tufts University in Medford, Massachusetts, and Harvard University, says this is typical. For example, sexual reproduction requires parental sperm and egg cells. Sometimes cells split or budded off from a parent.

“This is unique,” Blackiston says. These xenobots “find loose parts in the environment and cobble them together.” This second generation of xenobots can move like their parents, Blackiston says.
The researchers discovered that spheroid xenobots could only produce one more generation before dying out. The original xenobots' shape was predicted by an artificial intelligence program, allowing for four generations of replication.

A C shape, like an openmouthed Pac-Man, was predicted to be a more efficient progenitor. When improved xenobots were let loose in a dish, they began scooping up loose cells into their gaping “mouths,” forming more sphere-shaped bots (see image below). As many as 50 cells clumped together in the opening of a parent to form a mobile offspring. A xenobot is made up of 4,000–6,000 frog cells.

Petersen likes the Xenobots' small size. “The fact that they were able to do this at such a small scale just makes it even better,” she says. Miniature xenobots could sculpt tissues for implantation or deliver therapeutics inside the body.

Beyond the xenobots' potential jobs, the research advances an important science, says study coauthor and Tufts developmental biologist Michael Levin. The science of anticipating and controlling the outcomes of complex systems, he says.

“No one could have predicted this,” Levin says. “They regularly surprise us.” Researchers can use xenobots to test the unexpected. “This is about advancing the science of being less surprised,” Levin says.

The magnitude 5 earthquake was responsible for the discharge of energy that was 10 times greater than the previous record holder.

Any Martians who happen to be reading this should quickly learn how to duck and cover.

NASA's Jet Propulsion Laboratory in Pasadena, California, reported that on May 4, the planet Mars was shaken by an earthquake of around magnitude 5, making it the greatest Marsquake ever detected to this point. The shaking persisted for more than six hours and unleashed more than ten times as much energy as the earthquake that had previously held the record for strongest.

The event was captured on record by the InSight lander, which is operated by the United States Space Agency and has been researching the innards of Mars ever since it touched down on the planet in 2018 (SN: 11/26/18). The epicenter of the earthquake was probably located in the vicinity of Cerberus Fossae, which is located more than 1,000 kilometers away from the lander.

The surface of Cerberus Fossae is notorious for being broken up and experiencing periodic rockfalls. According to geophysicist Philippe Lognonné, who is the lead investigator of the Seismic Experiment for Interior Structure, the seismometer that is onboard the InSight lander, it is reasonable to assume that the ground is moving in that area. "This is an old crater from a volcanic eruption."

Marsquakes, which are similar to earthquakes in that they give information about the interior structure of our planet, can be utilized to investigate what lies beneath the surface of Mars (SN: 7/22/21). And according to Lognonné, who works at the Institut de Physique du Globe in Paris, there is a great deal that can be gleaned from analyzing this massive earthquake. Because the quality of the signal is so high, we will be able to focus on the specifics.

Quenched lava may have aided in the formation of long RNA strands required by primitive life.

It took a long time for life to emerge. Microbes were present 3.7 billion years ago, just a few hundred million years after the 4.5-billion-year-old Earth had cooled enough to sustain biochemistry, according to fossils, and many scientists believe RNA was the genetic material for these first species. RNA, while not as complicated as DNA, would be difficult to forge into the lengthy strands required to transmit genetic information, raising the question of how it may have originated spontaneously.

Researchers may now have a solution. They demonstrate how basaltic glasses assist individual RNA letters, also known as nucleoside triphosphates, join into strands up to 200 letters long in lab studies. The glasses are formed when lava is quenched in air or water, or when melted rock generated by asteroid strikes cools rapidly, and they would have been plentiful in the early Earth's fire and brimstone.

The outcome has caused a schism among top origin-of-life scholars. "This appears to be a great story that finally explains how nucleoside triphosphates react with each other to create RNA strands," says Thomas Carell, a scientist at Munich's Ludwig Maximilians University. However, Harvard University's Jack Szostak, an RNA expert, says he won't believe the results until the study team thoroughly describes the RNA strands.

Researchers interested in the origins of life like the idea of a primordial "RNA universe" since the molecule can perform two different functions that are essential for life. It's made up of four chemical letters, just like DNA, and can carry genetic information. RNA, like proteins, can catalyze chemical reactions that are necessary for life.

However, RNA can cause headaches. No one has yet discovered a set of plausible primordial conditions that would cause hundreds of RNA letters—each of which is a complicated molecule—to join together into strands long enough to support the intricate chemistry required to kick-start evolution.

Basaltic glasses may have played a role, according to Stephen Mojzsis, a geologist at the University of Colorado, Boulder. They're high in metals like magnesium and iron, which help to trigger a variety of chemical reactions. "Basaltic glass was omnipresent on Earth at the time," he adds.

He provided the Foundation for Applied Molecular Evolution samples of five different basalt glasses. Each sample was ground into a fine powder, sanitized, and combined with a solution of nucleoside triphosphates by molecular biologist Elisa Biondi and her colleagues. The RNA letters were unable to link up without the presence of glass powder. However, when the molecules were mixed with the glass particles, they formed long strands of hundreds of letters, according to the researchers, who published their findings in Astrobiology this week. There was no need for heat or light. Biondi explains, "All we had to do was wait." After only a day, little RNA strands produced, yet the strands continued to grow for months. Jan Paek, a molecular biologist at Firebird Biomolecular Sciences, says, "The beauty of this approach is its simplicity." "Mix the components together, wait a few days, and look for RNA."

Nonetheless, the findings pose a slew of problems. One of the questions is how nucleoside triphosphates came to be in the first place. Recent study by Biondi's colleague Steven Benner suggests that the same basaltic glasses may have aided in the creation and stabilization of individual RNA letters.

The form of the lengthy RNA strands, according to Szostak, is a significant challenge. Enzymes in modern cells ensure that most RNAs form long linear chains. RNA letters, on the other hand, can bind in complicated branching sequences. Szostak wants the researchers to reveal what kind of RNA was produced by the basaltic glasses. "It irritates me that the authors made an intriguing initial finding but then chose to follow the hype rather than the research," Szostak says.

Biondi acknowledges that her team's experiment almost probably results in some RNA branching. She does acknowledge, however, that some branched RNAs are seen in species today, and that analogous structures may have existed before the origin of life. Other studies carried out by the study also confirmed the presence of lengthy strands with connections, indicating that they are most likely linear. "It's a healthy argument," says Dieter Braun, a Ludwig Maximilian University origin-of-life chemist. "It will set off the next series of tests."

By Surojit Chatterjee, Chief Product Officer

2021 proved to be a breakout year for crypto with BTC price gaining almost 70% yoy, Defi hitting $150B in value locked, and NFTs emerging as a new category. Here’s my view through the crystal ball into 2022 and what it holds for our industry:

1. Eth scalability will improve, but newer L1 chains will see substantial growth — As we welcome the next hundred million users to crypto and Web3, scalability challenges for Eth are likely to grow. I am optimistic about improvements in Eth scalability with the emergence of Eth2 and many L2 rollups. Traction of Solana, Avalanche and other L1 chains shows that we’ll live in a multi-chain world in the future. We’re also going to see newer L1 chains emerge that focus on specific use cases such as gaming or social media.

2. There will be significant usability improvements in L1-L2 bridges — As more L1 networks gain traction and L2s become bigger, our industry will desperately seek improvements in speed and usability of cross-L1 and L1-L2 bridges. We’re likely to see interesting developments in usability of bridges in the coming year.

3. Zero knowledge proof technology will get increased traction — 2021 saw protocols like ZkSync and Starknet beginning to get traction. As L1 chains get clogged with increased usage, ZK-rollup technology will attract both investor and user attention. We’ll see new privacy-centric use cases emerge, including privacy-safe applications, and gaming models that have privacy built into the core. This may also bring in more regulator attention to crypto as KYC/AML could be a real challenge in privacy centric networks.

4. Regulated Defi and emergence of on-chain KYC attestation — Many Defi protocols will embrace regulation and will create separate KYC user pools. Decentralized identity and on-chain KYC attestation services will play key roles in connecting users’ real identity with Defi wallet endpoints. We’ll see more acceptance of ENS type addresses, and new systems from cross chain name resolution will emerge.

5. Institutions will play a much bigger role in Defi participation — Institutions are increasingly interested in participating in Defi. For starters, institutions are attracted to higher than average interest-based returns compared to traditional financial products. Also, cost reduction in providing financial services using Defi opens up interesting opportunities for institutions. However, they are still hesitant to participate in Defi. Institutions want to confirm that they are only transacting with known counterparties that have completed a KYC process. Growth of regulated Defi and on-chain KYC attestation will help institutions gain confidence in Defi.

6. Defi insurance will emerge — As Defi proliferates, it also becomes the target of security hacks. According to London-based firm Elliptic, total value lost by Defi exploits in 2021 totaled over $10B. To protect users from hacks, viable insurance protocols guaranteeing users’ funds against security breaches will emerge in 2022.

7. NFT Based Communities will give material competition to Web 2.0 social networks — NFTs will continue to expand in how they are perceived. We’ll see creator tokens or fan tokens take more of a first class seat. NFTs will become the next evolution of users’ digital identity and passport to the metaverse. Users will come together in small and diverse communities based on types of NFTs they own. User created metaverses will be the future of social networks and will start threatening the advertising driven centralized versions of social networks of today.

8. Brands will start actively participating in the metaverse and NFTs — Many brands are realizing that NFTs are great vehicles for brand marketing and establishing brand loyalty. Coca-Cola, Campbell’s, Dolce & Gabbana and Charmin released NFT collectibles in 2021. Adidas recently launched a new metaverse project with Bored Ape Yacht Club. We’re likely to see more interesting brand marketing initiatives using NFTs. NFTs and the metaverse will become the new Instagram for brands. And just like on Instagram, many brands may start as NFT native. We’ll also see many more celebrities jumping in the bandwagon and using NFTs to enhance their personal brand.

9. Web2 companies will wake up and will try to get into Web3 — We’re already seeing this with Facebook trying to recast itself as a Web3 company. We’re likely to see other big Web2 companies dipping their toes into Web3 and metaverse in 2022. However, many of them are likely to create centralized and closed network versions of the metaverse.

10. Time for DAO 2.0 — We’ll see DAOs become more mature and mainstream. More people will join DAOs, prompting a change in definition of employment — never receiving a formal offer letter, accepting tokens instead of or along with fixed salaries, and working in multiple DAO projects at the same time. DAOs will also confront new challenges in terms of figuring out how to do M&A, run payroll and benefits, and coordinate activities in larger and larger organizations. We’ll see a plethora of tools emerge to help DAOs execute with efficiency. Many DAOs will also figure out how to interact with traditional Web2 companies. We’re likely to see regulators taking more interest in DAOs and make an attempt to educate themselves on how DAOs work.

Thanks to our customers and the ecosystem for an incredible 2021. Looking forward to another year of building the foundations for Web3. Wagmi.