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ODU Scientists Observe Detailed Mechanism of Cell Contraction

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Scientists at Old Dominion University and the University of Leeds have observed the never-before-seen genesis of cell contraction. This process, known as “contractility” and fueled by a process called ATP hydrolysis, is critical to cell function. The breakthrough has implications for the treatment of conditions ranging from neuromuscular disorders to heart disease.

In their trailblazing paper, the scientists explain how they were able to examine the structural changes that occur upon binding between actin and myosin, the two proteins that provide mechanical energy for cellular contractility.  The research, “Swinging lever mechanism of actomyosin directly shown by time-resolved cryo-EM,” appeared April 9, 2025, in the journal Nature.

“The interaction between the rope-like protein filaments actin and myosin occurs in a fraction of a second, which has hampered efforts to visualize this process in detail until now,” says Howard White, Ph.D., professor of Biomedical and Translational Sciences at Eastern Virginia Medical School, part of Macon & Joan Brock Virginia Health Sciences at Old Dominion University. ODU is a top R1 research institution.

Dr. White’s team of scientists worked in collaboration with structural biologists from the University of Leeds to design and build a fast-freezing machine for cryo-electron microscopy that allowed them to observe the structural changes in the myosin molecule during its interaction with actin. The ability to see this process is central to understanding cellular contractility.

Dr. White and colleagues worked for more than a decade to develop the technology and to prove the concept that the machine could freeze samples in a millisecond time frame to see fast molecular interactions.

For Dr. White, the research represents the capstone for a 50-year scientific career in cellular kinetics.

“This work provided the technology to enable us to understand how actin and myosin convert the free energy from ATP hydrolysis into work in muscle and the mechanism of disease-causing myosin mutations that are associated with diseases affecting the heart, colon, and kidneys as well as neurological defects,” Dr. White said.

The conversion of chemical energy into mechanical work by actomyosin is described by the so-called “cross-bridge cycle.”  In cells, contraction is produced by the interaction between actin and myosin filaments and powered by the hydrolysis of ATP.  The actin-myosin complex is a molecular partnership that is involved in a variety of biological functions ranging from muscle contraction to cell division and organelle transportation within the cell.

The research was funded by grants from the National Institutes of Health, the Muscular Dystrophy Association and the American Heart. Dr. White’s lab members who contributed to the research were (pictured above) Betty Virok and Jenifer Atherton, along with his ODU colleagues Cristina Risi, PhD, instructor of Biomedical and Translational Sciences; Eva Forgacs, PhD, associate professor of Biomedical and Translational Sciences; and Vitold Galkin, PhD, associate professor of Biomedical and Translational Sciences.