The Dynamics of Dynamin

July 16, 2019

Researchers from the Technion’s Faculty of Biology have deciphered the action of dynamin, the protein in a process that allows the cell to internalize nutrients. The paper was recently published in the Proceedings of the National Academy of Sciences (PNAS).

Biological cells, just like the whole organism, cannot live without eating. Since they do not have a mouth, the cells developed a clever technique for the intake of cargo molecules into the cell, known as endocytosis.

In the endocytosis process, the cell membrane forms a bulge that develops and protrudes inwards. At the end of the process, a separate membrane shell, called a vesicle, forms inside the cell, in which the nutrients are trapped. To complete this process, it is necessary to cut the neck of the budding vesicle and separate it from the cell membrane. A central factor in this act of severing is a protein called dynamin. The dynamin molecules form a chain that tightens around the membrane neck of the bud and severs it, thus releasing the vesicle inside the cell.

The problem is that this internal process is very difficult to investigate, and even though it has been studied extensively, the mechanics of the process are still not clear. This is why the achievement of Technion researchers Assistant Professor Tom Shemesh and post-doctoral students Dr. Avihay Kadosh and Dr. Ben Yellin is so important. The model the trio proposed was verified experimentally by researchers at the University of Geneva using an atomic-force microscope (AFM).

Prof. Shemesh is a physicist by training. As a result, he approaches the study of biology by focusing on the physics and mechanics of biological processes. Postdoctoral researcher Dr. Avihay Kadosh, who completed his master’s degree in the Technion Department of Physics, took a similar path from physics from biology.

“The complex dynamics of the cell have many aspects of information processing. This information-centered perspective of biology is attractive for theoreticians, and is undoubtedly a very relevant and promising approach,” explained Prof. Shemesh. “But we focus rather on the mechanical aspects of cellular processes. In fact, we’re looking at “blue-collar work” — pushing, pulling and positioning of the proteins and other molecules. This was our approach for studying the helical structure of dynamin chains in this case.”

A helix is a recurring motif in the structure of living cells, from the renowned double helix of the DNA molecule — the dramatic discovery of Francis Crick, James Watson and Maurice Wilkins in 1953 — to internal features of many proteins and the large super-structures of the cell skeleton. Therefore, researchers say, it can be concluded that this is a structure that stems from basic principles, shared by many systems.

The dynamin chains that are part of the endocytosis process are also helical in shape, and the discovery by the Technion researchers is related to the tilt of the helix at its point of contact with the cell membrane. “In fact, we developed a physical model that relates the shape of the protein chain to the mechanical forces that develop in the structure,” said Prof. Shemesh. “This model showed that the shape and stability of the dynamin chain are largely determined by the angle of insertion of parts of the dynamin protein into the cell membrane. Using the model, we were also able to provide an explanation for a long-standing puzzle: why do the dynamin chains break-up during the process of membrane remodeling? We found that a change in the angle of insertion drives a partial disassembly of the chain.”

Following the findings, the researchers have presented a new geometric object: the tilted helix.

“Many classical geometries, such as helices, helicoids and catenoids, have been predicted and found in sub-cellular systems in the past.” said Prof. Shemesh. “Remarkably, in this case the reverse has happened: the characterization of the tilted helix was motivated by the underlying biology.”

The researchers found that the angle at which the dynamin protein is embedded in the membrane is critical to the success of the mission, namely, the task of cutting the membrane neck and breaking down the chain of dynamin to release the food inside the cell. Although the study focused on the dynamin molecules, the researchers believe that the considerations that led to the tilted helix model are “universal,” and that understanding them will lead to the explanation of other phenomena of protein-membrane interactions in the cell.

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