Insight into How Cells Get Signals from Physical Senses Could Lead to New Disease Treatments

The body’s cells are constantly receiving and reacting to signals from their environment. A lot is known about how a cell senses and responds to chemical signals, or biomolecules, such as COVID-19. But little is known about how signals from the physical environment, like touch, temperature or light, direct a cell’s activity. Understanding that process could lead to new ways of treating cancer and other disease.mage showing how the red mechano-chemical waves (actin waves) guide the signaling molecules (green). Image courtesy of UMD MURI team.mage showing how the red mechano-chemical waves (actin waves) guide the signaling molecules (green). Image courtesy of UMD MURI team.

A new study published May 1, 2023 in the Proceedings of the National Academy of Sciences by a University of Maryland-led Multidisciplinary University Research Initiative (MURI) funded by the Air Force Office of Scientific Research has opened the door to seeing how cells react to physical signals.

“We elucidated a cell's sense of touch,” said Professor Wolfgang Losert, a team leader of the study. “We think how cells sense the physical environment may be quite distinct from how they sense the chemical environment. This may help us develop new treatment options for conditions that involve altered physical cellular environments, such as tumors, immune disease and wound healing.”

A major difference between chemical and physical signals is size. Chemical signals are 100,000 times smaller than the width of a human hair. Physical cues are the heavyweights in the ring.

“We looked at how cells sense crucial physical cues from their environment that are on the order of 100 times larger than chemical signaling molecules,” said Losert, who also has a joint appointment in UMD’s Institute for Physical Science and Technology (IPST).

“We’re really answering a kind of long-standing mystery of how cells react to cues in their environment that are on a physical rather than chemical-size scale,” said paper co-author and MURI team member John T. Fourkas, a professor in UMD’s Department of Chemistry and Biochemistry with a joint appointment in IPST.

The MURI team studied the major players in a cell’s interaction with its physical environment: the cytoskeleton, a network of proteins that surround a cell and acts as a direct sensor of the physical environment; actin, the protein that keeps cells connected; and the cell’s signaling pathways.

Qixin Yang (Ph.D. ’22, physics), who led the experiments and analysis for her Ph.D. research at UMD, said, “I think our work related to the cytoskeleton shows that it plays an important role in sensing physical cues, like pain.”

The MURI team found that the networks that guide cell migration are upstream for chemical sensing and downstream for physical, topographic sensing; and that actin is the direct sensor for both types of signals.

“I think this is the first real crucial confirmation that actin itself is the sensor and that the waves are really where they are in the sensing pathway, not way downstream, but up front and center,” Fourkas said.

“Our findings reveal that, in much the same way that patterns of waves in the ocean allow an expert surfer to understand the undersea topography, the so-called ‘mechano-chemical’ waves in cells are key in sensing signals from their physical environment that are much larger than single proteins,” Losert said. “That has implications for how you might design physical interventions to change the behavior of cells.”

For instance, previous research by a co-author of this study, Peter Devreotes of Johns Hopkins University, found that actin dynamics were different for cancer cells considered most invasive.

“Understanding how drugs impact waves is an important additional piece of information that may be used in making decisions on treatment options,” Losert said. “I see our study also providing pointers on how you can improve the ability of immune cells to be guided to their target.”

The MURI team is made up of researchers in physics, chemistry, biology, bioengineering and dermatology from the University of Maryland and several other institutions.


In addition to Losert, Fourkas and Yang, UMD chemistry graduate student Matt Hourwitz was a co-author of the paper.

The paper, “Nanotopography modulates intracellular excitable systems through cytoskeleton actuation," was published in PNAS on May 1, 2023.

This research was supported by the Air Force Office of Scientific Research (Award No. FA9550-16-1-0052). This story does not necessarily reflect the views of this organization.

Original story by Ellen Ternes:


New Research Sheds Light on How Mesothelioma Develops

Mesothelioma has been a high-profile disease at the center of several multi-billion-dollar lawsuits, but the disease itself remains a medical mystery. 

The incurable cancer develops on the lining of many internal organs—including the lungs and peritoneum—but its symptoms are often undetectable until about 40 years after initial exposure to asbestos, a common and naturally occurring mineral. This long latency period, as well as cases of mesothelioma in individuals who have no known exposure to asbestos, has made the disease and its origins a longstanding puzzle to doctors and scientists alike. 

Now, an interdisciplinary team of researchers from the University of Maryland may have identified an essential piece of the puzzle. In a paper published online in the journal Environmental Research in January 2023, the team suggests that the key to understanding mesothelioma lies in how immune cells “sense” and interact with particles around them. 

According to the new study, the shape and size of contaminant particles, like asbestos fibers, significantly influence how the immune system responds after exposure—ultimately impacting health outcomes.An asbestos fiber (stained blue) in lung tissue being surrounded by macrophages. Image courtesy of the Centers for Disease Control and Prevention.An asbestos fiber (stained blue) in lung tissue being surrounded by macrophages. Image courtesy of the Centers for Disease Control and Prevention.

“The geometry or size of a particle is more important than its mineral composition when it comes to how likely it is to cause adverse health effects in patients,” explained study co-author and UMD Professor Emerita of Geology Ann Wylie. “Asbestos kicks up an immune response when the immune system is exposed to the right shape and size of particle.”

“We believe that the most dangerous types of fibers—ones that are particularly thin and long—likely cause immune cells called macrophages to recruit other immune cells to asbestos exposure sites within tissue. This response prevents the immune cells from reaching other places where they’re needed, like precancerous lesions,” added study co-author Wolfgang Losert, a professor in the Department of Physics and the Institute for Physical Science and Technology at UMD. “This could cause the immune system to effectively ignore other serious conditions around that organ.”

In a previous study, some members of the research team found that mineral particles with diameters less than 250 nanometers and lengths greater than 5 micrometers were more difficult for the lungs to physically clear out than their shorter counterparts. The longer particles stayed in the lungs longer, further interacting with healthy lung tissues before eventually encountering immune cells like macrophages.

For the new study, the researchers examined particles taken from mineral samples from various geological sites. They found that immune cells used a mechanism called esotaxis to “sense” physical features—such as size, shape and texture—of the particles around them and responded differently to each particle based on that information. 

The researchers observed that when macrophages encountered these small and dangerous types of particles (including smaller asbestos fibers), the macrophages “activated” to recruit other immune cells to the site. However, because these longer particles are less able to be removed physically, activated macrophages continue to call for more immune cells to the same site over a long period of time, dominating immune cell communication.

The researchers hypothesize that this eventual “hijacking” of the immune cell migration system would lead to other nearby regions of an infected organ to be neglected because all immune cells are delegated to a single site. As a result, those other tissues would be deprived of the immune system’s healing abilities—a possible explanation as to why many immunocompromised patients can develop mesothelioma even without known exposure to asbestos fibers.

In essence, a particle’s nanotopography—their surface features formed at a nanoscopic level—indirectly controls the internal machinery that allows immune cells to move.

“This response basically overwhelms the immune cell communication system and diverts the body’s own defenses away from where they’re needed,” explained study co-author John Fourkas, a professor in the UMD Department of Chemistry and Biochemistry and the Institute for Physical Science and Technology. “The physical characteristics of a mineral particle can change the behavior of immune cells in the long term, which could be why mesothelioma symptoms take a minimum of 30 to 40 years to manifest.” 

The team believes that their theory also applies to mineral particles that are similar in size to carcinogenic asbestos fibers, which could provide more insight into other diseases caused by such particles. With rising concerns about the carcinogenic properties of airborne mineral particles like crystalline silica and carbon nanotubes, additional information about esotaxis and its effects on immune responses could be the key to protection. 

“More research about the induction of cancer by minerals is still needed—it’s complicated and requires the expertise of geologists, chemists, physicists and bioscientists,” Wylie said. “But this project and others like it bring us a step closer to figuring out what mechanisms underlie not only mesothelioma but all types of cancer formations.”


Original story:

Additional UMD co-authors on the paper include Shuyao Gu, Abby Bull, Amilee Huang, Matt Hourwitz and Mona Abostate.

The study, “Excitable systems: A new perspective on the cellular impact of elongate mineral particles,” was published in Environmental Research on January 23, 2023.

This research was supported by the National Science Foundation (Award No. PHY2014151). This story does not necessarily reflect the views of this organization.

Alumna, Adjunct Elected to National Academy of Sciences

Alumna Ana Maria Rey and Adjunct Professor Paul Julienne were recently elected to the National Academy of Sciences.

Paul Julienne (Credit: Bailey Bedford/JQI)Paul Julienne (Credit: Bailey Bedford/JQI)“I am both gratified and humbled by this honor, which is only possible because of the many excellent colleagues and students with whom I have worked with over the years,” said Julienne, an emeritus Fellow of the Joint Quantum Institute. “I owe them a debt of gratitude, for it is by working together that science advances."

Julienne and Rey are among 120 new members elected this year, joining a prestigious group of more than 2,500 scientists around the country who have been elected by their peers in recognition of their research achievementsThe National Academy of Sciences also elected 23 new international scientist who are joining more than 500 other international members.

reyAna Maria Rey. Courtesy of the John D. and Catherine T. MacArthur Foundation

Julienne helped establish the research field of ultracold matter, which investigates atoms and molecules near absolute zero. His theoretical research includes developing models that describe how cold trapped molecules and atoms can be precisely controlled using magnetic fields or lasers. This research topic has revealed details of atomic states and chemical reactions of ultracold molecules.

Rey received a B.S. (1999) from the Universidad de los Andes in Bogotá and a Ph.D. (2004) from the University of Maryland, studying with Charles Clark. She is currently a JILA fellow and University of Colorado professor. Her research group focuses on ultracold atoms, optical lattices and the underlying physics of these systems, with applications in condensed matter and quantum information science. JILA is a research partnership between CU and NIST, In 2013, Rey was named a MacArthur Foundation Fellow

The National Academy of Sciences is a private, non-profit society of scholars that was established by an Act of Congress—signed by President Abraham Lincoln—in 1863. The organization works to further science in America and to provide analysis and advice to solve complex problems and inform public policy decisions.

JQI story by Bailey Bedford:

Department Rated Highly by US News

The Department of Physics received high ratings in the U.S. News & World Report’s 2024 Best Graduate Schools lists released on April 25. .Eleven programs and specialties in the University of Maryland’s College of Computer, Mathematical, and Natural Sciences (CMNS) earned top-25 accolades.

The college’s graduate rankings are:US News Best Grad SchoolsUS News Best Grad Schools

  • Physics at No. 17 (No. 6 among public institutions)
    • Atomic/molecular/optical specialty at No. 6
    • Quantum specialty at No. 9
    • Condensed matter specialty at No. 17
  • Computer Science at No. 17 (No. 10 among public institutions)
    • Artificial intelligence specialty at No. 15
    • Programming language specialty at No. 20
    • Systems specialty at No. 22
  • Mathematics at No. 20 (No. 6 among public institutions)
    • Applied math specialty at No. 15
    • Analysis specialty at No. 24
  • Earth Sciences at No. 27 (No. 16 among public institutions)
  • Chemistry at No. 46 (No. 27 among public institutions)
  • Biological Sciences at No. 68 (was not surveyed this year)

For a full account of the University's rankings:

The rankings are based on statistical surveys of more than 2,200 programs and reputation surveys sent to nearly 19,000 academics and professionals, conducted in fall 2022 and early 2023. U.S. News said this year that it placed a greater emphasis this year on outcomes, recognizing that students’ ultimate goal in attending graduate school is likely to become a practicing professional.