Researchers Show How Molecular Tug-of-war Gives Shape to Cells

University of Maryland researchers in a new study have demystified the process by which cells receive their shape—and it all starts with a protein called actin.

A key component of the cytoskeleton, actin provides structure to cells, much like how our skeletons support our bodies. But unlike a skeleton, actin cytoskeletons are highly malleable structures that can rapidly assemble and disassemble in response to biochemical and biophysical cues.

The findings, published Oct. 21 in the journal eLife, could have important implications for human health. Because actin rings are central to our bodies’ ability to fight off foreign cells—with defects potentially resulting in impaired immunity or autoimmune disorders—the study could aid the development of future drugs.

It is well known that actin can form both 3D spherical shell-like structures that protect cells from external pressure and 2D rings that modify intracellular functions. But whenever researchers tried to recreate these structures outside the cell, they almost always ended up with clusters of actin. No one knew why—until now.

The researchers used computer simulations to show that actin and its partner protein, myosin, engage in a tug-of-war, with myosin trying to trap actin in local clusters and actin attempting to flee. If actin wins, actin filaments escape myosin’s pulling force and spontaneously form rings and spherical shells. If myosin wins, the actin network collapses and forms dense clusters.

“Actin rings and spherical shells are ubiquitous in almost all cell types across species. We think that understanding the mechanism behind the formation of these structures unlocks the door to how cells sense and respond to their environment,” said Garegin Papoian, a co-author of the study and a UMD Monroe Martin Professor in the Department of Chemistry and Biochemistry and the Institute for Physical Science and Technology (IPST).

The research team also included Arpita Upadhyaya, a physics professor with a joint appointment in IPST, physics graduate student Kaustubh Wagh, biological sciences graduate student Aashli Pathni, biophysics graduate student Vishavdeep Vashisht, biophysics Ph.D. student Haoran Ni and Qin Ni Ph.D. ’21.