Tag Archives: Nanomachines

Nanoscientists speculate that artificial life forms could be medicine of the future

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Even after all these years, my jaw is still capable of dropping but then I read the details. This looks a lot like ‘medical nanobots’ which researchers have been talking about for a long time. Nice twist on a familiar theme. From an October 5, 2023 news item on ScienceDaily,

Imagine a life form that doesn’t resemble any of the organisms found on the tree of life. One that has its own unique control system, and that a doctor would want to send into your body. It sounds like a science fiction movie, but according to nanoscientists, it can—and should—happen in the future.

Creating artificial life is a recurring theme in both science and popular literature, where it conjures images of creeping slime creatures with malevolent intentions or super-cute designer pets. At the same time, the question arises: What role should artificial life play in our environment here on Earth, where all life forms are created by nature and have their own place and purpose?

Associate professor Chenguang Lou from the Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, together with Professor Hanbin Mao from Kent State University, is the parent of a special artificial hybrid molecule that could lead to the creation of artificial life forms. They have now published a review in the journal Cell Reports Physical Science on the state of research in the field behind their creation. The field is called “hybrid peptide-DNA nanostructures,” and it is an emerging field, less than ten years old.

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An October 5, 2023 University of Southern Denmark press release (also on EurekAlert) by Birgitte Svennevig, which originated the news item, shares the researcher’s (Chenguang Lou) vision for the research and more technical details about “hybrid peptide-DNA nanostructures” along with other international research efforts,

Lou’s vision is to create viral vaccines (modified and weakened versions of a virus) and artificial life forms that can be used for diagnosing and treating diseases.

“In nature, most organisms have natural enemies, but some do not. For example, some disease-causing viruses have no natural enemy. It would be a logical step to create an artificial life form that could become an enemy to them,” he says.

Similarly, he envisions such artificial life forms can act as vaccines against viral infection and can be used as nanorobots [also known as nanobots] or nanomachines loaded with medication or diagnostic elements and sent into a patient’s body.

“An artificial viral vaccine may be about 10 years away. An artificial cell, on the other hand, is on the horizon because it consists of many elements that need to be controlled before we can start building with them. But with the knowledge we have, there is, in principle, no hindrance to produce artificial cellular organisms in the future,” he says.

What are the building blocks that Lou and his colleagues in this field will use to create viral vaccines and artificial life? DNA and peptides are some of the most important biomolecules in nature, making DNA technology and peptide technology the two most powerful molecular tools in the nanotechnological toolkit today. DNA technology provides precise control over programming, from the atomic level to the macro level, but it can only provide limited chemical functions since it only has four bases: A, C, G, and T. Peptide technology, on the other hand, can provide sufficient chemical functions on a large scale, as there are 20 amino acids to work with. Nature uses both DNA and peptides to build various protein factories found in cells, allowing them to evolve into organisms.

Recently, Hanbin Mao and Chenguang Lou have succeeded in linking designed three-stranded DNA structures with three-stranded peptide structures, thus creating an artificial hybrid molecule that combines the strengths of both. This work was published in Nature Communications in 2022. (read the article here “Chirality transmission in macromolecular domains” and the press release at https://www.sdu.dk/en/om_sdu/fakulteterne/naturvidenskab/nyheder-2022/supermolekyle)

Elsewhere in the world, other researchers are also working on connecting DNA and peptides because this connection forms a strong foundation for the development of more advanced biological entities and life forms.

At Oxford University, researchers have succeeded in building a nanomachine made of DNA and peptides that can drill through a cell membrane, creating an artificial membrane channel through which small molecules can pass. (Spruijt et al., Nat. Nanotechnol. 2018, 13, 739-745)

At Arizona State University, Nicholas Stephanopoulos and colleagues have enabled DNA and peptides to self-assemble into 2D and 3D structures. (Buchberger et al., J. Am. Chem. Soc. 2020, 142, 1406-1416)

At Northwest University [Northwestern University?], researchers have shown that microfibers can form in conjunction with DNA and peptides self-assembling. DNA and peptides operate at the nano level, so when considering the size differences, microfibers are huge. (Freeman et al., Science, 2018, 362, 808-813)

At Ben-Gurion University of the Negev, scientists have used hybrid molecules to create an onion-like spherical structure containing cancer medication, which holds promise to be used in the body to target cancerous tumors. (Chotera et al., Chem. Eur. J., 2018, 24, 10128-10135)

“In my view, the overall value of all these efforts is that they can be used to improve society’s ability to diagnose and treat sick people. Looking forward, I will not be surprised that one day we can arbitrarily create hybrid nanomachines, viral vaccines and even artificial life forms from these building blocks to help the society to combat those difficult-to-cure diseases. It would be a revolution in healthcare,” says Chenguang Lou.

Here’s a link to and a citation for the latest paper,

Peptide-DNA conjugates as building blocks for de novo design of hybrid nanostructures by Mathias Bogetoft Danielsen, Hanbin Mao, Chenguang Lou. Cell Reports Physical Science Volume 4, Issue 10, 18 October 2023, 101620 DOI: https://doi.org/10.1016/j.xcrp.2023.101620

This paper is open access.

Inspired by Picasso (or Schumpeter, Shiva, and others?), Université de Montréal researchers employ creative destruction to create new nanomachines

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I associate the idea of ‘creative destruction’ with economics and Joseph Schumpeter but it is more widespread and has a much longer history (see more at the end of this posting).

Here we have Université de Montréal researchers being inspired by the idea from (what was to me) an unexpected source, from a February 9, 2023 news item on Nanowerk,

“Every act of creation,” Picasso famously noted, “is first an act of destruction.”

Taking this concept literally, researchers in Canada have now discovered that “breaking” molecular nanomachines basic to life can create new ones that work even better.

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I love this image. Bravo!

Researchers Dominic Lauzon and Alexis Vallée-Bélisle Credit: Amélie Philibert & Benoit Gougeon | Université de Montréal

A February 9, 2023 Université de Montréal news release, which originated the news item, delves further into this act of creative destruction,

Evolved over millions of years

Life on Earth is made possible by tens of thousands of nanomachines that have evolved over millions of years. Often made of proteins or nucleic acids, they typically contain thousands of atoms and are less than 10,000 times the size of a human hair.

“These nanomachines control all molecular activities in our body, and problems with their regulation or structure are at the origin of most human diseases,” said the new study’s principal investigator Alexis Vallée-Bélisle, a chemistry professor at Université de Montréal.

Studying the way these nanomachines are built, Vallée-Bélisle, holder of the Canada Research Chair in Bioengineering and Bio-Nanotechnology, noticed that while some are made using a single component or part (often long biopolymers), others use several components that spontaneously assemble.

“Since most of my students spend their lives creating nanomachines, we started to wonder if it is more beneficial to create them using one or more self-assembling molecular components,” said Vallée-Bélisle.

A ‘destructive’ idea

To explore this question, his doctoral student Dominic Lauzon, had the “destructive” idea of breaking up some nanomachines to see if they could be reassembled. To do so, he made artificial DNA-based nanomachines that could be “destroyed” by breaking them up.

“DNA is a remarkable molecule that offers simple, programmable and easy-to-use chemistry,” said Lauzon, the study’s first author. “We believed that DNA-based nanomachines could help answer fundamental questions about the creation and evolution of natural and human-made nanomachines.”

Lauzon and Vallée-Bélisle spent years performing the experimental validations. They were able to demonstrate that nanomachines could easily withstand fragmentation, but more importantly, that such a destructive event allowed for the creation of various novel functionalities, including different sensitivity levels towards variation in component concentration, temperature and mutations.

What the researchers found is that these functionalities could arise simply by controlling the concentration of each individual component. For example, when cutting a nanomachine in three components, nanomachines were found to activate more sensitively at high concentration of components. In contrast, at low concentration of components, nanomachines could be programmed to activate or deactivate at specific moment in time or to simply inhibit their function.

“Overall, these novel functionalities were created  by simply cutting up, or destroying, the structure of an existing nanomachine,” said Lauzon. “These functionalities could drastically improve human-based nanotechnologies such as sensors, drug carriers and even molecular computers”.

Evolving new functionalities

Just as Picasso typically destroyed dozens of unfinished works to create his famous artworks, and just like muscles need to break down to get stronger, and innovative new companies are born by eliminating older competitors from the market, nanoscale machines can evolve new functionalities by being taken apart.

Unlike common machines like cell phones, televisions and cars, which are made by combining components using screws and bolts, glue, solder or electronics, “nanomachines rely on thousands of weak dynamic intermolecular forces that can spontaneously reform, enabling broken nanomachines to re-assemble,” said Vallée-Bélisle.

In addition to providing nanotechnology researchers with a simple design strategy to create the next generation of nanomachines, the UdeM team’s findings also shed light on how natural molecular nanomachines may have evolved.

“Biologists have recently discovered that about 20 per cent of biological nanomachines may have evolved through the fragmentation of their genes,” said Vallée-Bélisle. “With our results, biologists now have a rational basis for understanding how the fragmentation of these ancestral proteins could have created new molecular functionalities for life on Earth.”

Here’s a link to and a citation for the paper,

Functional advantages of building nanosystems using multiple molecular components by D. Lauzon & A. Vallée-Bélisle. Nature Chemistry volume 15, pages 458–467 (2023) DOI: https://doi.org/10.1038/s41557-022-01127-4 Published online: 09 February 2023 Issue Date: April 2023

This paper is behind a paywall.

Creative destruction

The Wikipedia entry for ‘Creative destruction’ is primarily on economic theory and various philosophies with no mention of Picasso. However, there is a fascinating segue into Eastern mysticism,

Other early usage

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Hugo Reinert has argued that Sombart’s formulation of the concept was influenced by Eastern mysticism, specifically the image of the Hindu god Shiva, who is presented in the paradoxical aspect of simultaneous destroyer and creator.

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On that note, have a lovely weekend.

You need a quantum mechanic for an atom-sized machine

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This news comes from the National University of Singapore’s Centre for Quantum Technologies according to a May 4, 2020 news item on Nanowerk (Note: A link has been removed),

Here’s a new chapter in the story of the miniaturisation of machines: researchers in a laboratory in Singapore have shown that a single atom can function as either an engine or a fridge. Such a device could be engineered into future computers and fuel cells to control energy flows.

“Think about how your computer or laptop has a lot of things inside it that heat up. Today you cool that with a fan that blows air. In nanomachines or quantum computers, small devices that do cooling could be something useful,” says Dario Poletti from the Singapore University of Technology and Design (SUTD).

This work gives new insight into the mechanics of such devices. The work is a collaboration involving researchers at the Centre for Quantum Technologies (CQT) and Department of Physics at the National University of Singapore (NUS), SUTD and at the University of Augsburg in Germany. The results were published in the peer-reviewed journal npj Quantum Information (“Single-atom energy-conversion device with a quantum load”).

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The researchers have included an exceptionally pretty illustration with the press release,

Caption: Experiments with a single-atom device help researchers understand what quantum effects come into play when machinery shrinks to the atomic scale. Credit: Aki Honda / Centre for Quantum Technologies, National University of Singapore

A May 4, 2020 National University of Singapore press release (also on EurekAlert), which originated the news item, delves further into the work,

Engines and refrigerators are both machines described by thermodynamics, a branch of science that tells us how energy moves within a system and how we can extract useful work. A classical engine turns energy into useful work. A refrigerator does work to transfer heat, reducing the local temperature. They are, in some sense, opposites.

People have made small heat engines before using a single atom, a single molecule and defects in diamond. A key difference about this device is that it shows quantumness in its action. “We want to understand how we can build thermodynamic devices with just a few atoms. The physics is not well understood so our work is important to know what is possible,” says Manas Mukherjee, a Principal Investigator at CQT, NUS, who led the experimental work.

The researchers studied the thermodynamics of a single barium atom. They devised a scheme in which lasers move one of the atom’s electrons between two energy levels as part of a cycle, causing some energy to be pushed into the atom’s vibrations. Like a car engine consumes petrol to both move pistons and charge up its battery, the atom uses energy from lasers as fuel to increase its vibrating motion. The atom’s vibrations act like a battery, storing energy that can be extracted later. Rearrange the cycle and the atom acts like a fridge, removing energy from the vibrations.

In either mode of operation, quantum effects show up in correlations between the atom’s electronic states and vibrations. “At this scale, the energy transfer between the engine and the load is a bit fuzzy. It is no longer possible to simply do work on the load, you are bound to transfer some heat,” says Poletti. He worked out the theory with collaborators Jiangbin Gong at NUS Physics and Peter Hänggi in Augsburg. The fuzziness makes the process less efficient, but the experimentalists could still make it work.

Mukherjee and colleagues Noah Van Horne, Dahyun Yum and Tarun Dutta used a barium atom from which an electron (a negative charge) is removed. This makes the atom positively charged, so it can be more easily held still inside a metal chamber by electrical fields. All other air is removed from around it. The atom is then zapped with lasers to move it through a four-stage cycle.

The researchers measured the atom’s vibration after applying 2 to 15 cycles. They repeated a given number of cycles up to 150 times, measuring on average how much vibrational energy was present at the end. They could see the vibrational energy increasing when the atom was zapped with an engine cycle, and decreasing when the zaps followed the fridge cycle.

Understanding the atom-sized machine involved both complicated calculations and observations. The team needed to track two thermodynamic quantities known as ergotropy, which is the energy that can be converted to useful work, and entropy, which is related to disorder in the system. Both ergotropy and entropy increase as the atom-machine runs. There’s still a simple way of looking at it, says first author and PhD student Van Horne, “Loosely speaking, we’ve designed a little machine that creates entropy as it is filled up with free energy, much like kids when they are given too much sugar.”

Here’s a link to and a citation for the paper,

Single-atom energy-conversion device with a quantum load by Noah Van Horne, Dahyun Yum, Tarun Dutta, Peter Hänggi, Jiangbin Gong, Dario Poletti & Manas Mukherjee. npj Quantum Information volume 6, Article number: 37 (2020) Published: 01 May 2020

This paper is open access.

McGill University team gets better understanding of nonribosomal peptide synthetases (NRPSs) also described as nanomachines

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This research from McGill University (Montréal, Canada) focuses on enzymes and their possible utility as nanomachines for producing drugs. (For the uninitiated, nano means billionth, which, in turn, means these enzymes are measured at the nanoscale.)

An April 30, 2020 McGill University news release (also on EurekAlert) describes the work,

Many of the drugs and medicines that we rely on today are natural products taken from microbes like bacteria and fungi. Within these microbes, the drugs are made by tiny natural machines – mega-enzymes known as nonribosomal peptide synthetases (NRPSs). A research team led by McGill University has gained a better understanding of the structures of NRPSs and the processes by which they work. This improved understanding of NRPSs could potentially allow bacteria and fungi to be leveraged for the production of desired new compounds and lead to the creation of new potent antibiotics, immunosuppressants and other modern drugs.

“NRPSs are really fantastic enzymes that take small molecules like amino acids or other similar sized building blocks and assemble them into natural, biologically active, potent compounds, many of which are drugs,” said Martin Schmeing, Associate Professor in the Department of Biochemistry at McGill University, and corresponding author on the article that was recently published in Nature Chemical Biology. “An NRPS works like a factory assembly line that consists of a series of robotic workstations. Each station has multi-step workflows and moving parts that allow it to add one building block substrate to the growing drug, elongating and modifying it, and then passing it off to the next little workstation, all on the same huge enzyme.”

Ultra-intensive light beam allows scientists to see proteins

n their paper featured on the cover of the May 2020 issue of Nature Chemical Biology, the team reports visualizing an NRPS mechanical system by using the CMCF beamline at the Canadian Light Source (CLS). The CLS is a Canadian national lab [these types of labs are sometimes called synchrotrons] that produces the ultra-intense beams of X-rays required to image proteins, as even mega-enzymes are too small to see with any light microscope.

“Scientists have long been excited about the potential of bioengineering NRPSs by identifying the order of building blocks and reorganizing the workstations in the enzyme to create new drugs, but the effort has rarely been successful,” said Schmeing. “This is the first time anyone has seen how these enzymes transform keto acids into a building block that can be put into a peptide drug. This helps us understand how the NRPSs can use so very many building blocks to make the many different compounds and therapeutics.”

Here’s a link to and a citation for the paper,

Structural basis of keto acid utilization in nonribosomal depsipeptide synthesis by Diego A. Alonzo, Clarisse Chiche-Lapierre, Michael J. Tarry, Jimin Wang & T. Martin Schmeing. Nature Chemical Biology volume 16, pages493–496(2020) Published: 17 February 2020

This paper is behind a paywall.

Training drugs

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This summarizes some of what’s happening in nanomedicine and provides a plug (boost) for the  University of Cambridge’s nanotechnology programmes (from a June 26, 2017 news item on Nanowerk),

Nanotechnology is creating new opportunities for fighting disease – from delivering drugs in smart packaging to nanobots powered by the world’s tiniest engines.

Chemotherapy benefits a great many patients but the side effects can be brutal.
When a patient is injected with an anti-cancer drug, the idea is that the molecules will seek out and destroy rogue tumour cells. However, relatively large amounts need to be administered to reach the target in high enough concentrations to be effective. As a result of this high drug concentration, healthy cells may be killed as well as cancer cells, leaving many patients weak, nauseated and vulnerable to infection.

One way that researchers are attempting to improve the safety and efficacy of drugs is to use a relatively new area of research known as nanothrapeutics to target drug delivery just to the cells that need it.

Professor Sir Mark Welland is Head of the Electrical Engineering Division at Cambridge. In recent years, his research has focused on nanotherapeutics, working in collaboration with clinicians and industry to develop better, safer drugs. He and his colleagues don’t design new drugs; instead, they design and build smart packaging for existing drugs.

The University of Cambridge has produced a video interview (referencing a 1966 movie ‘Fantastic Voyage‘ in its title)  with Sir Mark Welland,

A June 23, 2017 University of Cambridge press release, which originated the news item, delves further into the topic of nanotherapeutics (nanomedicine) and nanomachines,

Nanotherapeutics come in many different configurations, but the easiest way to think about them is as small, benign particles filled with a drug. They can be injected in the same way as a normal drug, and are carried through the bloodstream to the target organ, tissue or cell. At this point, a change in the local environment, such as pH, or the use of light or ultrasound, causes the nanoparticles to release their cargo.

Nano-sized tools are increasingly being looked at for diagnosis, drug delivery and therapy. “There are a huge number of possibilities right now, and probably more to come, which is why there’s been so much interest,” says Welland. Using clever chemistry and engineering at the nanoscale, drugs can be ‘taught’ to behave like a Trojan horse, or to hold their fire until just the right moment, or to recognise the target they’re looking for.

“We always try to use techniques that can be scaled up – we avoid using expensive chemistries or expensive equipment, and we’ve been reasonably successful in that,” he adds. “By keeping costs down and using scalable techniques, we’ve got a far better chance of making a successful treatment for patients.”

In 2014, he and collaborators demonstrated that gold nanoparticles could be used to ‘smuggle’ chemotherapy drugs into cancer cells in glioblastoma multiforme, the most common and aggressive type of brain cancer in adults, which is notoriously difficult to treat. The team engineered nanostructures containing gold and cisplatin, a conventional chemotherapy drug. A coating on the particles made them attracted to tumour cells from glioblastoma patients, so that the nanostructures bound and were absorbed into the cancer cells.

Once inside, these nanostructures were exposed to radiotherapy. This caused the gold to release electrons that damaged the cancer cell’s DNA and its overall structure, enhancing the impact of the chemotherapy drug. The process was so effective that 20 days later, the cell culture showed no evidence of any revival, suggesting that the tumour cells had been destroyed.

While the technique is still several years away from use in humans, tests have begun in mice. Welland’s group is working with MedImmune, the biologics R&D arm of pharmaceutical company AstraZeneca, to study the stability of drugs and to design ways to deliver them more effectively using nanotechnology.

“One of the great advantages of working with MedImmune is they understand precisely what the requirements are for a drug to be approved. We would shut down lines of research where we thought it was never going to get to the point of approval by the regulators,” says Welland. “It’s important to be pragmatic about it so that only the approaches with the best chance of working in patients are taken forward.”

The researchers are also targeting diseases like tuberculosis (TB). With funding from the Rosetrees Trust, Welland and postdoctoral researcher Dr Íris da luz Batalha are working with Professor Andres Floto in the Department of Medicine to improve the efficacy of TB drugs.

Their solution has been to design and develop nontoxic, biodegradable polymers that can be ‘fused’ with TB drug molecules. As polymer molecules have a long, chain-like shape, drugs can be attached along the length of the polymer backbone, meaning that very large amounts of the drug can be loaded onto each polymer molecule. The polymers are stable in the bloodstream and release the drugs they carry when they reach the target cell. Inside the cell, the pH drops, which causes the polymer to release the drug.

In fact, the polymers worked so well for TB drugs that another of Welland’s postdoctoral researchers, Dr Myriam Ouberaï, has formed a start-up company, Spirea, which is raising funding to develop the polymers for use with oncology drugs. Ouberaï is hoping to establish a collaboration with a pharma company in the next two years.

“Designing these particles, loading them with drugs and making them clever so that they release their cargo in a controlled and precise way: it’s quite a technical challenge,” adds Welland. “The main reason I’m interested in the challenge is I want to see something working in the clinic – I want to see something working in patients.”

Could nanotechnology move beyond therapeutics to a time when nanomachines keep us healthy by patrolling, monitoring and repairing the body?

Nanomachines have long been a dream of scientists and public alike. But working out how to make them move has meant they’ve remained in the realm of science fiction.

But last year, Professor Jeremy Baumberg and colleagues in Cambridge and the University of Bath developed the world’s tiniest engine – just a few billionths of a metre [nanometre] in size. It’s biocompatible, cost-effective to manufacture, fast to respond and energy efficient.

The forces exerted by these ‘ANTs’ (for ‘actuating nano-transducers’) are nearly a hundred times larger than those for any known device, motor or muscle. To make them, tiny charged particles of gold, bound together with a temperature-responsive polymer gel, are heated with a laser. As the polymer coatings expel water from the gel and collapse, a large amount of elastic energy is stored in a fraction of a second. On cooling, the particles spring apart and release energy.

The researchers hope to use this ability of ANTs to produce very large forces relative to their weight to develop three-dimensional machines that swim, have pumps that take on fluid to sense the environment and are small enough to move around our bloodstream.

Working with Cambridge Enterprise, the University’s commercialisation arm, the team in Cambridge’s Nanophotonics Centre hopes to commercialise the technology for microfluidics bio-applications. The work is funded by the Engineering and Physical Sciences Research Council and the European Research Council.

“There’s a revolution happening in personalised healthcare, and for that we need sensors not just on the outside but on the inside,” explains Baumberg, who leads an interdisciplinary Strategic Research Network and Doctoral Training Centre focused on nanoscience and nanotechnology.

“Nanoscience is driving this. We are now building technology that allows us to even imagine these futures.”

I have featured Welland and his work here before and noted his penchant for wanting to insert nanodevices into humans as per this excerpt from an April 30, 2010 posting,
Getting back to the Cambridge University video, do go and watch it on the Nanowerk site. It is fun and very informative and approximately 17 mins. I noticed that they reused part of their Nokia morph animation (last mentioned on this blog here) and offered some thoughts from Professor Mark Welland, the team leader on that project. Interestingly, Welland was talking about yet another possibility. (Sometimes I think nano goes too far!) He was suggesting that we could have chips/devices in our brains that would allow us to think about phoning someone and an immediate connection would be made to that person. Bluntly—no. Just think what would happen if the marketers got access and I don’t even want to think what a person who suffers psychotic breaks (i.e., hearing voices) would do with even more input. Welland starts to talk at the 11 minute mark (I think). For an alternative take on the video and more details, visit Dexter Johnson’s blog, Nanoclast, for this posting. Hint, he likes the idea of a phone in the brain much better than I do.

I’m not sure what could have occasioned this latest press release and related video featuring Welland and nanotherapeutics other than guessing that it was a slow news period.