Cell shape is determined by the molecular tug-of-war between actin and myosin
The method by which cells acquire their shape has been clarified in a recent study by experts from the University of Maryland, and it all begins with a protein called actin.
In a manner similar to how our skeletons support our bodies, actin is an essential part of the cytoskeleton that gives cells structure. The actin cytoskeleton, in contrast to our skeleton, is a very elastic structure that can quickly come together and fall apart in response to pharmacological and biophysical signals.
Actin can both form 2D rings that alter intracellular processes and 3D spherical shell-like structures that shield cells from pressure. However, if scientists attempted to duplicate similar structures outside of the cell, they almost always came up with actin clusters. Until now, no one was aware of the cause.
The researchers demonstrated through computer simulations that actin and myosin, the protein that it partners with, engage in a tug-of-war, with actin attempting to escape and myosin attempting to confine it in local clusters. If actin wins, actin filaments are freed from myosin’s grip and form spherical shells and rings on their own. Actin network collapses and creates dense clusters if myosin prevails.
“In practically every type of cell across all animals, actin rings and spherical shells are present. The key to understanding how cells sense and react to their environment, in our opinion, is found in the mechanism underlying the formation of these structures “Co-author of the study and Monroe Martin Professor at the University of Maryland in the Department of Chemistry and Biochemistry and the Institute for Physical Science and Technology, Garegin Papoian (IPST).
The research may have significant health ramifications. The results of this study could help the creation of future medications because actin rings are crucial to our bodies’ capacity to fight off foreign cells, with abnormalities potentially leading to decreased immunity or autoimmune illnesses.
Actin filaments, which resemble trains, are created when actin monomers join together. The treadmilling mechanism causes these actin trains to move throughout the cell. The myosin motors, which direct trains in opposing directions toward one another, are also in action. According to Papoian, Qin Ni (Ph.D. ’21, chemical engineering), and Ph.D. candidate in biophysics Haoran Ni, the creation of actin rings was caused by a conflict between the pulling force of myosin and the rate of treadmilling.
Since it is impossible to fine-tune these parameters in living cells, the researchers used a simulation program called MEDYAN, created by the Papoian Lab. MEDYAN simulates the movements of cytoskeletal proteins by applying physics and chemical laws. They created a thin disk and spherical shell to replicate an actin and myosin network (also known as actomyosin).
They discovered that actin trains that move slowly experience traffic jams, or actomyosin clusters, that have been seen in networks assembled outside of cells. However, if the actin trains travel quickly, they can elude the pull of myosin. Myosin’s pulling action causes the actin trains to spin once they approach the disk’s edge, preventing them from colliding directly with it. All the trains move in a circle around the disk’s edge as a result of the repetition of these events, forming the actin ring.
A thermodynamic hypothesis is presented in further study to explain why cells form rings and shells. The lowest energy configuration is preferred by systems, according to the rules of physics. Actin filaments are bent by myosin proteins, which store mechanical energy that must be released before actin can unwind. In living cells, the development of rings or shells, which are the lowest energy structure according to thermodynamics, is made possible by actin’s ability to move quickly enough to avoid myosin and run to the edge.
Rings weren’t previously visible outside the cell because actin wasn’t flowing quickly enough, according to Papoian. “Myosin was winning ten out of ten times.”
The team focused on T cells, where rings naturally form, to test this model in living cells with the help of Arpita Upadhyaya, a UMD physics professor with a joint appointment in IPST, physics graduate student Kaustubh Wagh, biological sciences graduate student Aashli Pathni, and biophysics graduate student Vishavdeep Vashisht.
Our bodies’ T cells are responsible for hunting alien cells. The cytoskeleton of T cells quickly reorganizes to form an actin ring at the cell-cell contact when they become activated and detect a cell as foreign. The researchers used high-resolution live-cell imaging to examine the impact of perturbing actin and myosin starting with cells that had formed rings.
In striking agreement with related models, decreasing the actin train speed caused the ring to dissolve into tiny clusters while increasing the pulling force of myosin caused the ring to rapidly compress.
The team intends to expand the model’s complexity and incorporate additional cytoskeletal elements and organelles as a follow-up to this research.
According to Papoian, “We have been able to capture one key component of cytoskeletal architecture.” We intend to use fundamental ideas from physics and chemistry to piece together a computational model of an entire cell.
Qin Ni et al. (2022), A tug of war between filament treadmilling and myosin induced contractility generates actin ring, eLife. DOI: 10.7554/eLife.82658. https://elifesciences.org/articles/82658
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