Researchers at Michigan State University in East Lansing are using a first of its kind nanoparticle-based in vivo (in living organisms) imaging technique that could one day help diagnose and treat cancer. MSU is working with researchers from Johns Hopkins and Stanford universities.
The technique captures mechanical properties in living subjects that probe relationships between physics and in living organisms’ biology. The researchers developed tiny particles that, once inside living cells, can reveal information about cell structure, including how tumor cells physically change as they form a tumor.
“We engineered the ability to measure and quantify the nanomechanical properties of individual living cells within the body of a living animal for the first time,” says Bryan Smith, associate professor of biomedical engineering at MSU.
In a study earlier this year, Smith and his team designed nanoparticles that helped eat away plaque buildup in arteries. His new technique uses different nanoparticles that can be embedded into various cell types, including cancerous breast cells, in live animals. Analyzing how the particles move within the cell can reveal a lot about its internal physical properties.
“There previously existed no method to examine mechanical properties in living subjects – for example, in mammals – with high spatial resolution,” Smith says. “Such techniques promise to open entirely new avenues of inquiry for both disease diagnosis and treatment.”
The mechanical properties of biological tissues have been known to play a major role in many disease states, including heart disease, inflammation, and cancer, as well as normal physiology such as cell migration and organism development. The team first used nanoparticles to compare the mechanical properties between cells in culture, both standard 2-D and 3-D, and in live animals.
Tracking the cell movement revealed that the environment in which the cells are observed greatly affects their mechanical properties, which could mean that certain cell models may not be such valid representations of live animals.
“This tells cancer scientists interested in cancer mechanics that 2-D conditions may poorly replicate, and that certain 3-D conditions get substantially closer, to mimicking conditions within the live mouse,” Smith says.
The next part of the experiment looked at what actually happens to the internal structure of cancer cells as they begin to form tumors. Previous methods couldn’t answer the question because they were too invasive to test in living subjects.
By observing the movement of the nanoparticles within the cells, the team measured how soft the cells were. They found that normal cells’ pliability remained steady over time, but as cancer cells formed a tumor over the period of a week, they stiffened.
“We found that as a tumor begins to form in a living mouse, individual tumor cells mechanically stiffen,” Smith says. “This is a fundamental finding which is ultimately likely to have implications for cancer spread (metastasis) and tumor lethality. The discovery was made possible by integrating state-of-the-art imaging and particle tracking technologies from our and our collaborators’ labs.”
In the future, nanoparticles might be used to monitor the health of cells and the types of changes they undergo in disease processes. They might also be able to alter the course of diseases.
The team plans to look at the formation and dissemination of cancer metastases, which cause about 90 percent of cancer deaths.
“I hope one day we’ll be able to treat the physics of metastasis,” Smith says. “But we must first understand the mechanics and how changing them impacts cell behavior. We’re now looking into this.”
The findings were published in the journal Materials Today.
Another Research Team at MSU is studying octopuses to see if they hold the key to restoring limb function in humans with the use of smart prosthetics.
Galit Pelled, a neuroscientist and neuroengineer, has received a $2.35 million National Institutes of Health grant to analyze the impulses that drive the complex movements of an octopus’ eight arms. She believes the research could help create prosthetics humans can control with their brains, allowing them to regain the use of arms and hands.
“By studying the octopus, we may be able to give people back the use of their arms – to be able to pick up a cup or hold a child – which would be an amazing gift,” says Pelled, professor and director of the Neuroengineering Division at MSU’s Institute for Quantitative Health Sciences and Engineering.
Pelled and her team will be studying the relatively small California octopus, four of which reside in separate saltwater tanks equipped with waterproof motion capture cameras. Using video recordings and artificial intelligence, the researchers are gathering information on how an octopus waves its tentacles and grabs objects.
The movement information is gathered by electrodes implanted in the octopus’ arms. Artificial intelligence software is then used to follow, analyze, and characterize the motion.
“Each arm of an octopus contains an axial nerve that functions like a vertebrate’s spinal cord, yet with a limitless range of movement,” Pelled says. “This is why the octopus provides an unparalleled model to study central sensorimotor circuits associated with grasping behavior. If these movements can be described in mathematical terms, it may be possible to create an arm brace that a person could control with their brain.”
She says the work will help scientists study species toward the development of intelligent sensors, methods, and frameworks to acquire high dimensional biological data.
“The octopus is amazing in many ways,” Pelled says. “It has three hearts, blue-colored blood, it changes skin color for camouflaging and communication, and it completely regenerates its arms after injury. And now, it may give people reuse of their limbs.”
In Related News, the College of Osteopathic Medicine at Michigan State University in East Lansing is launching a physician assistant master’s degree program, set to begin next summer. Individuals can begin applying now. Physician assistants help meet the rising demand for health care workers.
“The whole profession came out of a need for rural health care in the 1960s,” says John McGinnity, professor in the College of Osteopathic Medicine and director of the new PA program. “During World War II, medical training was successfully accelerated to three years to meet demands for more doctors. Physicians realized you could accelerate medical school, train these health professionals, and get them out into the workforce earlier.”
PAs are trained to be medical generalists, which is often cited as one of the reasons the profession continues to grow and why PAs often switch specialties throughout their careers. They must recertify every 10 years, just like physicians. With the COVID-19 pandemic, PAs from all medical specialties are being called to work in emergency rooms.
The program, which will include four semesters in the classroom and one year of clinical rotations, will take place over 27 months. Unlike the majority of PA programs, MSU PA students will complete 48 percent of their instructional coursework alongside medical students.
“I see our role as PAs as the ultimate patient advocate,” McGinnity says. “A PA is the person who is supposed to get the team working together. From our profession’s conception, we were all about a team-based approach to medicine.”
McGinnity and his colleagues used MSU’s Hub for Innovation in Learning and Technology to create a curriculum. During the process, they reached out to major health care systems to find out where most PA graduates are strong and where there’s room for improvement.
MSU has applied to the Accreditation Review Commission on Education for the Physician Assistant, and a decision is scheduled to be made on provisional accreditation status at the September 2020 ARC-PA meeting.
Applications for May 2021 enrollment will be accepted until Jan. 15, 2021 and are available here. The program will be capped at 32 students for the inaugural class. McGinnity says there are usually eight-10 applications for every PA program seat.