Exploring the Mechanics of Life’s Tiniest Machines

Maria Mukhina hopes to shine a new light on how the intricate machinery of life works at its most fundamental level. 

With a background in physics, optics and nanotechnology, the assistant professor of physics who joined the University of Maryland in January 2024 studies how cells use mechanical energy to organize themselves and carry out their jobs—both when they’re healthy and when they’re not. Mukhina develops nanoscale tools to visualize and quantify the mechanical forces within cell nuclei. Her work focuses on the mechanical information processing in DNA and chromosomes, which could lead to a better understanding of gene expression, disease mechanisms and how complex structures like tissues form. Maria MukhinaMaria Mukhina

“Physics is just as important for controlling cell physiology as chemicals and genes,” Mukhina explained. “Yet, we know very little about the mechanics that emerge when millions of molecules come together in larger dynamic structures like the genome or cytoskeleton. This is due to the lack of appropriate tools that would allow us to read out the properties of these mechanics—and that is where my work comes in.”

Physics Chair Steven Rolston said Mukhina’s research will provide UMD students with new perspectives on how physics can be applied to many other disciplines, from biology to materials science. 

“Dr. Mukhina’s training in the optical physics of nanocrystals gives her unique insights in applying techniques based in physics to study genome mechanobiology—the interplay of mechanical forces with biological function,” Rolston said. “We are delighted to have her join our biological physics effort in the department.”

Using tiny tools to solve big mysteries

Growing up in Russia, Mukhina had no idea she would eventually pursue an academic career in physics. Raised in a family of musicians, engineers and doctors, she had no lab or research experience until she entered ITMO University in St. Petersburg as an undergraduate studying laser physics. 

“I was in third year of my undergraduate education when I finally realized that I could be working in a research lab looking for answers to a real scientific question,” she recalled. “Ever since then, I’ve been in love with experimental work in the lab. Nothing can compare with sitting there in the dark, doing some microscopy work and knowing something that no one else under the sun knows—it’s like pure magic!”

Mukhina brought that sense of wonder to her graduate studies at ITMO University, earning a master’s degree in photonics and optical computer science and a Ph.D. in optics. Her doctoral research focused on the new optical properties arising in spatially ordered ensembles of anisotropic nanocrystals, tiny semiconductor particles with unique properties that can be controlled by changing the size and shape of a nanocrystal. 

After that, Mukhina wanted to explore more biological applications for this rapidly evolving technology, so she joined the lab of Harvard University cell biologist Nancy Kleckner as a postdoc.

“The Kleckner lab introduced me to the world of cellular mechanics,” Mukhina said. “We viewed chromosomes as mechanical objects rather than carriers of genetic information. This perspective led me to a whole new world of questions about how physical forces can shape the behavior of cells. I was fascinated by the idea that one can use nanotools to do work in a living cell, to change how it performs its functions, and also how this branch of research draws so heavily from physics, cell biology, chemistry and more.”

The interdisciplinary nature of that work led Mukhina to look for research environments that could provide a space for both collaborative research and innovative thinking. She found the perfect new home for her research at UMD.   

“I wanted to find a place where I could interact with very diverse faculty and resources,” Mukhina said. “And beyond the university, I am also close to many cutting-edge research hubs like the U.S. National Science Foundation and the National Institutes of Health. I’m very excited to join a group with such varied expertise.”

 Now, Mukhina’s biggest research challenge is to accurately measure nanoscopic forces without disrupting the delicate environment of living cells. Drawing on her background in physics and nanotechnology, she develops tiny probes that can be directly introduced into cells to map out the forces at work within them. 

One probe is based on a concept called “DNA origami”—a technique that uses complementarity of two DNA strands to fold them into specific shapes. Another probe relies on a phenomenon called mechanoluminescence, where mechanical stresses applied to a material cause it to emit light. Both tools are designed to respond to the minute mechanical forces generated by mammalian cells, allowing researchers to create very detailed 4D maps of the intracellular force fields, which, as the researchers hypothesize, are used by the cells to orchestrate changes across microns of space, a huge distance in the cell universe. 

“All of this requires very fast and gentle to the cells light microscopy, so I’m also currently building a custom microscopy setup that will allow me to measure fluorescence or mechanoluminescence in events that occur within milliseconds,” Mukhina said. 

Mukhina also sees potential long-term applications for her research in medicine and beyond.

“Understanding the mechanics of how cells divide and segregate DNA could provide insights into cancer development or help us learn how to restart regeneration of our heart muscle cells after birth,” she explained. “My goal is for my work to open new avenues into developing regenerative therapies—and to push the boundaries of what we know about these physical forces that shape life itself.”

How Does Quantum Mechanics Meet Up With Classical Physics?

In physics, there is a deep disparity between the quantum and classical perspective on physical laws. Classical mechanics is used to describe the familiar world around us. This is the physics that you may have been exposed to in high school or early college where you calculate the trajectory of a baseball or speed of a car.  Quantum mechanics on the other hand is primarily used to describe incredibly small objects that are on sub-micron length scales such as electrons or atoms. Quantum mechanics is typically far from intuitive and is home to a variety of mind-bending phenomena like quantum tunneling and entanglement.  The differences between classical mechanics and quantum mechanics are quite striking.Schematic of the Aharonov-Bohm mesoscopic device connected to two electron reservoirs.  The device is biased by a magnetic flux and contains a “dephasing” trapping site. Schematic of the Aharonov-Bohm mesoscopic device connected to two electron reservoirs. The device is biased by a magnetic flux and contains a “dephasing” trapping site.

Everyday processes are governed by equations of motion that include friction, which creates the phenomenon of irreversibility, which we all take for granted.  Irreversibility becomes clear when we take a movie of an egg falling onto a solid surface and cracking open.  When the movie is run backward, we can tell that it is obviously “wrong” because broken eggs don’t spontaneously re-assemble and then jump up to the original location above the surface.  We say that irreversibility creates the perception of the “arrow of time.”  However, in quantum mechanics there is no “arrow of time” because all microscopic processes are fully irreversible – in other words in the microscopic world everything is the same for time running forward or backward.  The natural question to ask is then: how do the laws of quantum mechanics segue into those of classical mechanics as you involve increasing numbers of interacting particles and influences?

Semiclassical physics aims to bridge this disparity by exploring the regime between pure quantum evolution and classical physics. By introducing the corrupting influence of “dephasing”, one can disrupt the symmetric forward/backward time evolution and recover some degree of classical behavior from a quantum system, such as an electron travelling through a metal.  Of particular interest is whether this (typically undesired) “de-phasing” effect creates opportunities for new technologies that can perform tasks that are impossible in either the fully quantum or fully classical limits.

The mechanism of “dephasing”, the way a quantum system is pushed towards being classical, is then of great importance and needs to be understood.  In a recent experiment performed at the University of Maryland, it was found that one current theoretical treatment of “dephasing” effectively renders the model system classical, suggesting that more nuanced notions are required to understand what happens in this interesting semiclassical regime.

Photograph of the Aharonov-Bohm-graph microwave analogue made up of coaxial cables, circulators (small boxes), phase trimmers, and attenuators (large boxes). Photograph of the Aharonov-Bohm-graph microwave analogue made up of coaxial cables, circulators (small boxes), phase trimmers, and attenuators (large boxes). One hypothetical technology proposed to take advantage of this regime is a two-lead mesoscopic (i.e. really small) electrical device which would have a net charge current flowing through it in the absence of a potential difference without the use of a superconductor, in apparent violation of the second law of thermodynamics, also known as the law of no free lunch. The device in question is an Aharonov-Bohm (AB) ring with two electrical leads, shown in Fig. 1, which could be connected to large reservoirs of electrons. By tailoring the quantum properties of the ring one can create a situation in which electron waves that enter the ring at lead 1 only traverse the ring one time before they exit at lead 2, while the electron waves which start at lead 2 must traverse the ring three times before they can exit at lead 1. A localized “dephasing” center can be thought of as a trapping site that grabs a passing electron and holds on to it for a random amount of time before releasing it, having erased any information about where the electron came from or where it was going.  The released electron is then equally likely to exit the device through either lead.  Since the site will act preferentially on the longer lingering electrons, it would cause more electrons to travel from 1 to 2 than from 2 to 1, resulting in a net electrical current through the device with no external work being done!

The team at UMD has performed an experiment to address certain aspects of this provocative proposal. Though the experiment is fully classical, the team successfully established the transmission time imbalance using wave interference properties.  The UMD researchers made use of their recently developed concept of complex time delay to create a microwave circuit that had the necessary ingredients to mimic the asymmetric transmission-time properties of the hypothetical device.  This device is considered to be “classical” because it’s about the size of two human hands, in contrast to the originally proposed semiclassical device which would be the size of a few molecules. The device is a microwave circuit in the shape of a ring made mainly out of coaxial cables (see Fig. 2). The UMD researchers send microwave light pulses through the device to mimic electrons.  This analogue allows them to probe certain aspects of this provocative proposal and test their viability. 

Since they are working with a classical analogue they were limited in their ability to recreate the trapping site.  The researchers crudely attempted to mimic a quantum “dephasing” site by using a microwave attenuator. An attenuator works by reducing the energy (amplitude) of the microwave pulse and basically functions as a source of friction for the pulses.  The circuit was carefully studied and subjected to every kind of input the researchers could throw at it: frequency domain continuous waves, time domain pulses, and even broadband noise.Comparison of the Aharonov-Bohm-graph microwave analogue asymmetric transmission (purple diamonds and lines, P_21-P_12 on left axis) and simulated mesoscopic device transmission probability asymmetry (black circles, P_21-P_12 on right axis), as a function of microwave dissipation (Γ_A/2) in Nepers, and quantum “dephasing rate” (average number of inelastic scattering events per electron passage), on a common log scale. Comparison of the Aharonov-Bohm-graph microwave analogue asymmetric transmission (purple diamonds and lines, P_21-P_12 on left axis) and simulated mesoscopic device transmission probability asymmetry (black circles, P_21-P_12 on right axis), as a function of microwave dissipation (Γ_A/2) in Nepers, and quantum “dephasing rate” (average number of inelastic scattering events per electron passage), on a common log scale.

The experiment does indeed show an imbalance in the transmission probability through the classical analog microwave device.  Further, the UMD scientists find remarkably similar transmission imbalance as a function of the classical rate of imitated “dephasing” as quantum simulations show on the electron “dephasing” rate in a numerical simulation in the literature, see Fig. 3. These results suggest that the utilized treatment of “dephasing” does not adequately capture the quantum nature of the system, as the predicted effects can be seen in a purely classical system.  The team concludes that more sophisticated theoretical notions are required to understand what happens in the transition between pure quantum and classical physics.  Nevertheless, there seems to be unique opportunities to study new physics and technologies in quantum systems that interact with external degrees of freedom.

The experiments were done by graduate students Lei Chen, Isabella Giovannelli, and Nadav Shaibe in the laboratory of Prof. Steven Anlage in the Quantum Materials Center in the Physics Department at the University of Maryland.  Their paper is now published in Physical Review B (https://doi.org/10.1103/PhysRevB.110.045103).

LZ Experiment Sets New Record in Search for Dark Matter

Figuring out the nature of dark matter, the invisible substance that makes up most of the mass in our universe, is one of the greatest puzzles in physics. New results from the world’s most sensitive dark matter detector, LUX-ZEPLIN (LZ), have narrowed down possibilities for one of the leading dark matter candidates: weakly interacting massive particles, or WIMPs. 

LZ, led by the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), hunts for dark matter from a cavern nearly one mile underground at the Sanford Underground Research Facility in South Dakota. The experiment’s new results explore weaker dark matter interactions than ever searched before and further limit what WIMPs could be. UMD faculty Carter Hall and Anwar Bhatti contributed to the new results, along with Maryland graduate students John Armstrong, Eli Mizrachi, Ethan Ritchey, Bramwell Shafer, and Donghee Yeum. LZ’s central detector, the time projection chamber, in a surface lab clean room before delivery underground. Credit: Matthew Kapust/Sanford Underground Research Facility LZ’s central detector, the time projection chamber, in a surface lab clean room before delivery underground. Credit: Matthew Kapust/Sanford Underground Research Facility

“These are new world-leading constraints by a sizable margin on dark matter and WIMPs,” said Chamkaur Ghag, spokesperson for LZ and a professor at University College London (UCL). He noted that the detector and analysis techniques are performing even better than the collaboration expected. “If WIMPs had been within the region we searched, we’d have been able to robustly say something about them. We know we have the sensitivity and tools to see whether they’re there as we search lower energies and accrue the bulk of this experiment’s lifetime.” 

The collaboration found no evidence of WIMPs above a mass of 9 gigaelectronvolts/c2 (GeV/c2). (For comparison, the mass of a proton is slightly less than 1 GeV/c2.) The experiment’s sensitivity to faint interactions helps researchers reject potential WIMP dark matter models that don’t fit the data, leaving significantly fewer places for WIMPs to hide. The new results were presented at two physics conferences on August 26: TeV Particle Astrophysics 2024 in Chicago, Illinois, and LIDINE 2024 in São Paulo, Brazil. A scientific paper will be published in the coming weeks.

The results analyze 280 days’ worth of data: a new set of 220 days (collected between March 2023 and April 2024) combined with 60 earlier days from LZ’s first run. The experiment plans to collect 1,000 days’ worth of data before it ends in 2028.

“If you think of the search for dark matter like looking for buried treasure, we’ve dug almost five times deeper than anyone else has in the past,” said Scott Kravitz, LZ’s deputy physics coordinator and a professor at the University of Texas at Austin. “That’s something you don’t do with a million shovels – you do it by inventing a new tool.”

LZ’s sensitivity comes from the myriad ways the detector can reduce backgrounds, the false signals that can impersonate or hide a dark matter interaction. Deep underground, the detector is shielded from cosmic rays coming from space. To reduce natural radiation from everyday objects, LZ was built from thousands of ultraclean, low-radiation parts. The detector is built like an onion, with each layer either blocking outside radiation or tracking particle interactions to rule out dark matter mimics. And sophisticated new analysis techniques help rule out background interactions, particularly those from the most common culprit: radon.

This result is also the first time that LZ has applied “salting” – a technique that adds fake WIMP signals during data collection. By camouflaging the real data until “unsalting” at the very end, researchers can avoid unconscious bias and keep from overly interpreting or changing their analysis.

“We’re pushing the boundary into a regime where people have not looked for dark matter before,” said Scott Haselschwardt, the LZ physics coordinator and a recent Chamberlain Fellow at Berkeley Lab who is now an assistant professor at the University of Michigan. “There’s a human tendency to want to see patterns in data, so it’s really important when you enter this new regime that no bias wanders in. If you make a discovery, you want to get it right.”

 Members of the LZ collaboration gather at the Sanford Underground Research Facility in June 2023, shortly after the experiment began the recent science run. (Credit: Stephen Kenny/Sanford Underground Research Facility) Members of the LZ collaboration gather at the Sanford Underground Research Facility in June 2023, shortly after the experiment began the recent science run. (Credit: Stephen Kenny/Sanford Underground Research Facility)Dark matter, so named because it does not emit, reflect, or absorb light, is estimated to make up 85% of the mass in the universe but has never been directly detected, though it has left its fingerprints on multiple astronomical observations. We wouldn’t exist without this mysterious yet fundamental piece of the universe; dark matter’s mass contributes to the gravitational attraction that helps galaxies form and stay together.

LZ uses 10 tonnes of liquid xenon to provide a dense, transparent material for dark matter particles to potentially bump into. The hope is for a WIMP to knock into a xenon nucleus, causing it to move, much like a hit from a cue ball in a game of pool. By collecting the light and electrons emitted during interactions, LZ captures potential WIMP signals alongside other data.

“We’ve demonstrated how strong we are as a WIMP search machine, and we’re going to keep running and getting even better – but there’s lots of other things we can do with this detector,” said Amy Cottle, lead on the WIMP search effort and an assistant professor at UCL. “The next stage is using these data to look at other interesting and rare physics processes, like rare decays of xenon atoms, neutrinoless double beta decay, boron-8 neutrinos from the sun, and other beyond-the-Standard-Model physics. And this is in addition to probing some of the most interesting and previously inaccessible dark matter models from the last 20 years.”

LZ is a collaboration of roughly 250 scientists and engineers from 38 institutions in the United States, United Kingdom, Portugal, Switzerland, South Korea, and Australia; much of the work building, operating, and analyzing the record-setting experiment is done by early career researchers. The collaboration is already looking forward to analyzing the next data set and using new analysis tricks to look for even lower-mass dark matter. Scientists are also thinking through potential upgrades to further improve LZ, and planning for a next-generation dark matter detector called XLZD.

“Our ability to search for dark matter is improving at a rate faster than Moore’s Law,” Kravitz said. “If you look at an exponential curve, everything before now is nothing. Just wait until you see what comes next.”

Original story: https://newscenter.lbl.gov/2024/08/26/lz-experiment-sets-new-record-in-search-for-dark-matter/

LZ is supported by the U.S. Department of Energy, Office of Science, Office of High Energy Physics and the National Energy Research Scientific Computing Center, a DOE Office of Science user facility. LZ is also supported by the Science & Technology Facilities Council of the United Kingdom; the Portuguese Foundation for Science and Technology; the Swiss National Science Foundation, and the Institute for Basic Science, Korea. Over 38 institutions of higher education and advanced research provided support to LZ. The LZ collaboration acknowledges the assistance of the Sanford Underground Research Facility.

High School Student Earns Accolades for Summer Research with Gorshkov Group

Jason Youm, a high school student who performed summer research with Alexey Gorshkov, an adjunct associate professor of physics at UMD, in 2023, placed in the top dozen competitors in the physics and astronomy category at the Regeneron International Science and Engineering Fair (ISEF). In the competition, Youm, who recently completed his junior year at Montgomery Blair High School in Silver Spring, Maryland, presented research he completed under the mentorship of Gorshkov and Joseph Iosue, a graduate student in physics at UMD.

The Regeneron ISEF brings together high school students from across the world who earn their spots by qualifying at local science fairs. In his project, Youm performed calculations to help researchers investigate how quantum computers can perform certain tasks significantly faster than their traditional counterparts.

“I'm truly, really thankful for the research opportunity,” Youm said. “I think it's honestly changed my life. It's truly an invaluable experience.”Jason YoumJason Youm

Youm had harbored an interest in quantum physics for the first couple of years of high school, and after finishing his first calculus class during his sophomore year, he decided to look for opportunities to explore the interest more deeply. 

“Kind of on a whim, in mid-May, I just emailed some professors at UMD, because I heard they had a good program in quantum physics,” Youm said. “I just asked like, ‘I'm interested in these fields. Would you be interested in having a student intern during the summer?’ And Alexey was kind enough to accept me into the group.”

Gorshkov first looked over the relevant experience in math and physics Youm shared in his email and then reached out to the other members of the group to ask if any of them had a suitable project.

One of those graduate students, Iosue, was particularly interested in mentoring someone since he knew firsthand how valuable such experiences can be. When he was an undergraduate at the Massachusetts Institute of Technology (MIT), he had spent a summer working in Gorshkov’s group.

“My time as an undergrad in Alexey’s group was a very good experience for me,” Iosue said. “It was the best research experience I had until I started my Ph.D. So, I wanted to do something similar for someone else.”

Iosue remembered a project from his early days as a graduate student that had a natural continuation. The group hadn’t followed up on the possibility yet, and he thought the remaining work might be a suitable project for a motivated high school student.

The project developed mathematical tools for studying quantum entanglement—a phenomenon where the evolving fates of quantum particles become inextricably linked. A collection of quantum states can have different amounts of quantum entanglement that are possible, and Iosue performed calculations that help quantify if the quantum entanglement values are tightly or loosely clumped together. Entanglement plays a central role in quantum computers, so it is likely to be a key ingredient in any proof that quantum computing’s advantage is real and that a cleverly designed program on a traditional computer can’t possibly compete. 

The calculations that Iosue had performed were only the first of a set that each provide slightly different insights about the entanglement of the analyzed states. Iosue suggested that Youm could perform the other calculations by using the previous work as a guide. Gorshkov agreed, and Youm ended up taking on the project.

“My hope was that the calculations would be similar—like the whole beginning to end process that we did would be similar,” Iosue said. “So, it seemed like a high school student wouldn't have to necessarily dive into too much scientific literature or dive into too much uncertainty. I was hoping there was a bit more of a straight path, but with research, it's not always what you expect.”

Early in the summer, the project hit a snag. Iosue suggested Youm begin with a scientific paper that provided equations that were the natural starting point for the new calculations. But as Youm worked, his results weren’t going anywhere. When the group dug deeper, they determined that the equations in the paper were incorrect, and they had to start over by deriving the initial equations themselves.

Eventually, Youm successfully worked through the math for an additional portion of the calculations, and he also used computer simulations to verify his results.

“In the middle of the project was a lot of coding, mathematical work, and trying to understand the physics processes behind all the math that I was doing,” Youm said. “I worked for around eight hours a day, just trying to progress in my work and deriving the necessary formulas and the theorems. So it was pretty intensive, but also I really enjoyed it.”

In Youm’s science fair project, titled “Measuring Quantum Entanglement Entropy in Gaussian Boson Sampling,” he presented the results and discussed their practical applications to quantum experiments. The calculations apply to Gaussian boson sampling experiments where several measurements collect a sample of results from a specific set of prepared quantum states. Quantum mechanics allows a sample to be designed so that it reflects very specific statistics, and many physicists believe that for many cases it can be prohibitively complex for any computer not exploiting quantum phenomena to create a sample with the correct statistics.

The calculations that Youm performed are not directly used in sampling experiments, but they are a potential tool for studying how entanglement relates to the complexity of the sampling task. Understanding entanglement could be central to definitively proving if a sampling experiment has truly achieved an unassailable quantum advantage.

After the summer, Youm continued to work with the group—scheduling meetings around his normal school schedule and assignments. During the school year, Youm took the lead on writing a paper about the results, which the group has posted on the arXiv preprint server

“I've had high school students working with my group in the past, but this was the first time we worked over the summer with a rising junior instead of a rising senior,” said Gorshkov. “Jason's performance was outstanding!”

This summer Youm is once again took on a research project, but this year he was at the 2024 Center for Excellence in Education Research Science Institute summer program at MIT, which accepts 100 high school students from around the world. 

“I am really thankful for Alexey, and the rest of the research group, because without them I wouldn't have been able to get any of these opportunities,” Youm said. “I owe all of this to them, and I just feel really happy and grateful.”

Written by Bailey Bedford

 

In addition to Gorshkov and Iosue, QuICS Hartree Postdoctoral Fellow Yuxin Wang and JQI graduate student Adam Ehrenberg also worked with Youm and are authors on the paper posted on the arXiv preprint server.