Biological complexity: intracellular organization (Introduction)

by David Turell , Tuesday, November 24, 2020, 23:44 (1248 days ago) @ David Turell

Amazing details are appearing, but not yet complete:

https://knowablemagazine.org/article/living-world/2020/what-is-liquid-liquid-phase-sepa...

Biologists have studied these cellular processes for decades.

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"But at the crucial in-between scale, a big question mark remains: How do the right proteins organize themselves in a sea of fluid swarming with millions of molecules? Do they bump into each other by chance, or does the cell actively organize its fluid space to bring the correct partners together?

"The latter appears to be true, according to recent research at the intersection of physics and biology. Over the last decade, cell biologists have come to appreciate what many believe to be a whole new way that cells shape their internal landscape. Like blobs merging, then dispersing, in a lava lamp, or a salad dressing that separates into bubbles of oil and vinegar, groups of proteins can sometimes congeal into distinct droplets. One key way these droplets form is through a process called liquid-liquid phase separation.

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"Liquid-liquid phase separation is a relatively new concept for cell biologists, notwithstanding a few observations of liquid droplets in cells over the years, including one from more than a century ago. But in the physics world it’s old news — which is handy. “The power of this is that it sits on almost 100 years of condensed matter physics,” says biophysicist Alex Holehouse of Washington University in St. Louis,

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"Structurally, the proteins within a condensate are a bit like a tangle of cooked spaghetti, if you can imagine spaghetti strands made of weak Velcro. They bind lightly to many parts of the other proteins in the condensate, in no particular orientation. (Contrast that with the key-in-a-lock kind of binding that occurs when an enzyme attaches to a target or a chemical sticks to a receptor.) Many of the proteins or protein regions that make these weak connections are what biochemists call disordered, meaning they don’t take on a firm three-dimensional shape like most proteins do. The sum of all those weak forces holds the droplet together.

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"...a team led by biophysicist Michael Rosen at the University of Texas Southwestern Medical Center reported that proteins in a test tube could undergo phase separation to form droplets. The study showed that this phenomenon, which physicists and chemists have observed in many different molecules, occurs in proteins that can bind many targets.

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"The biggest, broadest hypothesis for the function of these droplets is that they concentrate specific sets of proteins and other molecules so as to house, kick-start or speed up the reactions the proteins engage in.

"For example, concentrating certain proteins in droplets near the cell membrane intensifies signals to assemble the cell’s cytoskeleton, the mesh of filaments that gives a cell its 3-D shape, as Rosen’s team reported in 2019. The phase separation may rev up a molecular process that normally ticks over barely above idle, the researchers proposed.

"And work from geneticist Richard Young’s lab at the Massachusetts Institute of Technology suggests that phase separation concentrates droplets of proteins needed to turn on the activity of genes or prod a chromosome to start copying itself at the correct places on the DNA strand. Rather than relying on chance for the right proteins to appear where they are needed, the droplets form what Young calls “a goody bag” of all the components that are necessary for these processes to occur.

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“'I think there’s no doubt that phase separation plays a very important role for cells,” she says. Researchers so far have identified at least 20 different types of phase-separated droplets, each consisting of different proteins and other molecules and emerging under different circumstances.

"Some condensates, like P granules, are long-standing characters in the cell, newly identified as products of phase separation. Others are just emerging. The diversity is not surprising, says Lee: Just like cell organelles that are bounded by membranes all have different functions, membraneless ones probably do too."

Comment: Cells are manufacturing factories and they have to be organized just like production lines, but they don't appear that way to the naked eye; just sloppy soups. I had a course in physical chemistry in 1953!! Why has biology research just beginning to catch up? Try to tell me this was not designed!!!!