Biological complexity: cellular manufacturing controls: (Introduction)

by David Turell , Thursday, January 07, 2021, 19:07 (1416 days ago) @ David Turell

How to coordinate protein enzyme reactions in packed cells:

https://www.quantamagazine.org/molecular-condensates-in-cells-may-hold-keys-to-lifes-re...

"Imagine packing all the people in the world into the Great Salt Lake in Utah — all of us jammed shoulder to shoulder, yet also charging past one another at insanely high speeds. That gives you some idea of how densely crowded the 5 billion proteins in a typical cell are, said Anthony Hyman, a British cell biologist and a director of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden.

"Somehow in that bustling cytoplasm, enzymes need to find their substrates, and signaling molecules need to find their receptors, so the cell can carry out the work of growing, dividing and surviving. If cells were sloshing bags of evenly mixed cytoplasm, that would be difficult to achieve. But they are not. Membrane-bounded organelles help to organize some of the contents, usefully compartmentalizing sets of materials and providing surfaces that enable important processes, such as the production of ATP, the biochemical fuel of cells. But, as scientists are still only beginning to appreciate, they are only one source of order.

"Recent experiments reveal that some proteins spontaneously gather into transient assemblies called condensates, in response to molecular forces that precisely balance transitions between the formation and dissolution of droplets inside the cell. Condensates, sometimes referred to as membraneless organelles, can sequester specific proteins from the rest of the cytoplasm, preventing unwanted biochemical reactions and greatly increasing the efficiency of useful ones. These discoveries are changing our fundamental understanding of how cells work.

"For instance, condensates may explain the speed of many cellular processes. “The key thing about a condensate — it’s not like a factory; it’s more like a flash mob. You turn on the radio, and everyone comes together, and then you turn it off and everyone disappears,” Hyman said.

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"These condensates aren’t just novel but thought-provoking: The idea that their functions emerge from the collective behaviors of the molecules has become the central concept in condensate biology, and it contrasts sharply with the classic picture of pairs of biochemical agents and their targets fitting together like locks and keys. Researchers are still figuring out how to probe the functionality of these emergent properties; that will require the development of new techniques to measure and manipulate the viscosity and other properties of tiny droplets in a cell.

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"These condensates aren’t just novel but thought-provoking: The idea that their functions emerge from the collective behaviors of the molecules has become the central concept in condensate biology, and it contrasts sharply with the classic picture of pairs of biochemical agents and their targets fitting together like locks and keys. Researchers are still figuring out how to probe the functionality of these emergent properties; that will require the development of new techniques to measure and manipulate the viscosity and other properties of tiny droplets in a cell.

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"Ribosomes are cells’ protein-making factories, and the number of them in a cell often limits its rate of growth. Work by Brangwynne and others suggests that fast-growing cells might get some help from the biggest condensate in the nucleus: the nucleolus. The nucleolus facilitates the rapid transcription of ribosomal RNAs by gathering up all of the required transcription machinery, including the specific enzyme (RNA polymerase I) that makes them.

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"The ATP was preventing protein aggregation at the concentrations found in living cells.

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"The chemist noted that in industrial processes, additives called hydrotropes are used to increase the solubility of hydrophobic molecules. Returning to his lab, Hyman and his colleagues found that ATP worked exceptionally well as a hydrotrope.

"Intriguingly, ATP is a very abundant metabolite in cells, with a typical concentration of 3-5 millimolar. Most enzymes that use ATP operate efficiently with concentrations three orders of magnitude lower. Why, then, is ATP so concentrated inside cells, if it isn’t needed to drive metabolic reactions?

"One candidate explanation, Hyman suggests, is that ATP doesn’t act as a hydrotrope below 3-5 millimolar. “One possibility is that in the origin of life, ATP might have evolved as a biological hydrotrope to keep biomolecules soluble in high concentration and was later co-opted as energy,” he said.

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"Protein aggregates can also solve problems that require very quick physiological responses, like stopping bleeding after injury."

Comment: To understand the point of this article with which I have just given a skimmed view, reread the introduction. In a lab a human controls each substance added one by one in any reaction. A cell is organized soup with multiple side-by-side reaction The design of the complex processes is extremely detailed. Never by chance. The article is at the lay reader level. Read it.