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How a protein turns around

Researchers have found that the protein ATP synthase, which plays a central role in the process of cellular respiration, organizes itself in a triangular pattern, because it is trapped in the vortex field it itself produces

The motors that simulate ATP synthase move in disorder and create an orderly structure with the help of the flow.
The motors that simulate ATP synthase move in disorder and create an orderly structure with the help of the flow.

Soft materials are physical systems that deform, or their structure changes easily, when an external force is applied to them. Soft substances include liquids, suspensions, emulsions, polymers, foam, gel and biological systems such as skin, blood, muscles, cells and proteins, in short: everything that is not solid and crystalline. These materials are essential for a variety of applications, including construction and packaging materials, foam, glue, cleaning and cosmetic materials, paints, food additives, lubricants and fuel additives.

What is the question? What is the secret of the self-organization of the main protein responsible for cellular energy production?

Dr. Naomi Oppenheimer, a physicist from the School of Physics and Astronomy at Tel Aviv University, studies soft materials and their characteristic properties, such as elasticity and flow. This, in order to understand how they work and produce metamaterials - with new properties that can be controlled and changed as needed. "Many times the research questions that deal with soft materials are biological, but we are actually examining their mechanical properties. It is possible, for example, to see how much the soft material shrinks, twists or flows - and observe the movements of cells and particles under a microscope. Most of the questions I deal with are related to the flow of the soft substances - for example, of blood cells in the veins and of proteins on the surface of cells - which makes it possible to understand physiological phenomena and study diseases."

From the simulations: the dots represent the ATP synthase proteins and you can see their self-organization (on the left all at the same speed and on the right at two different speeds).

In their latest research, which won a grant from the National Science Foundation, Dr. Oppenheimer and her team examined proteins that move across the cell membrane (the membrane that surrounds the cell), and in particular the ATP synthase protein. This protein is found in the membrane of the mitochondria, where it produces ATP (the "fuel" needed by the cells of the body, for their function and maintenance). It is actually a kind of small and efficient engine that produces energy in the form of ATP molecules and which is a main part of the cellular respiration process. According to Dr. Oppenheimer, "ATP synthase rotates very quickly on the surface of the mitochondrial membrane, creating a vortex around it. Experiments have shown that it arranges itself on its own in an orderly pattern, so the question arises, how was this order created, in such a chaotic flow?".

In all methods - in equations, simulations and experiments - the researchers discovered that ATP synthase proteins arrange themselves in an orderly pattern.

The researchers examined this question with several methods. First they wrote the equations of motion of the ATP synthase proteins and then tested them in computer simulations (which presented particles simulating the proteins). "We included the important components of the problem - the vortex flow and the way ATP synthase proteins repel their neighbors, other proteins, so as not to collide with them - and tried to solve it. Thanks to the simulation, we discovered the movements of the proteins and the eddies they create," explains Dr. Oppenheimer. Then, in experiments in the laboratory, the researchers built plastic motors with a propeller, which were several centimeters in size, operated them in a viscous liquid (oil), and watched the eddies that formed around them (thus obtaining another visualization of ATP synthase proteins and their movement in the membrane).

From the experiments: the motors that simulate ATP synthase move in disorder and create an orderly structure with the help of the flow.

In all methods - in equations, simulations and experiments - the researchers discovered that ATP synthase proteins arrange themselves in an orderly pattern. In the simulations it was also seen that if some proteins rotate quickly and some slowly, they split into two populations. "We started with a mixture of proteins and at the end of the simulation they separated from themselves - the fast proteins formed a small circle, and outside it the slow proteins rotated. In other words, it was found that these proteins are separated, which can be used to study a technique for separating proteins or particles in industry (for the production of medicines, for example)", notes Dr. Oppenheimer.

It was later found that ATP synthase arranges itself in an orderly pattern due to geometrical conservation: "thousands of membrane proteins stay in the same area thanks to the vortex. She creates a field that imprisons them there, and that's what makes them get along. This, in addition to their naturally occurring conflicts. And so, in such an orderly structure, they do not compete for resources in their environment and can produce more cellular energy", concludes Dr. Oppenheimer.

Life itself:

Dr. Naomi Oppenheimer, 39, married (to a physicist) + child (3), lives in Tel Aviv. In her spare time she likes to climb mountains, ride rollerblades and do aerial acrobatics.

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