Biological complexity: secret life of cells (Introduction)

by David Turell @, Friday, October 29, 2021, 15:30 (882 days ago) @ David Turell

The new amazing techniques seeing cell's molecules:

https://www.nature.com/articles/d41586-021-02904-w

"In recent years, imaging techniques such as cryo-ET have started to enable scientists to see biological molecules in their native environments. Unlike older methods that take individual proteins out of their niches to study them, these techniques provide a holistic view of proteins and other molecules together with the cellular landscape. Although they still have limitations — some researchers say that the resolution of cryo-ET, for example, is too low for molecules to be identified with certainty — the techniques are increasing in popularity and sophistication. Researchers who turn to them are not only mesmerized by the beautiful images, but also blown away by some of the secrets that are being revealed — such as the tricks bacteria use to infect cells or how mutated proteins drive neurodegenerative diseases such as Parkinson’s.

"Every peek through the microscope is another chance to explore uncharted cellular terrain, says Grant Jensen, a structural biologist at the California Institute of Technology in Pasadena. “There’s definitely a great joy in being able to see something for the first time,” he says.

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"Its early proponents sought a technique that could view biological molecules not only in fine detail, but also as they would look inside cells. Like cryo-EM, cryo-ET requires an electron microscope and relies on a sample preparation method known as vitrification: the rapid cooling of the water around a sample so that it freezes into a glass-like state, rather than as ice crystals. Unlike conventional cryo-EM, however, which requires purified samples, investigators can use cryo-ET to capture these molecules in situ.

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"And this is how proteins live, after all. “Proteins are social — at any given time a protein is in a complex with about ten other proteins,” says Villa. After viewing such interactions with cryo-ET, “I could not stomach the thought of myself studying another protein in isolation,” she adds.

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"Early demonstrations of cryo-ET from Baumeister’s group included snapshots1 of the cells of Dictyostelium, a bacteria-guzzling amoeba that lives in soil. The team revealed, among other things, previously unseen characteristics of intricate protein networks that make up the amoeba’s cytoskeleton — such as how individual filaments interact with one another and attach to specific structures on the membranes of Dictyostelium cells.

”'You can rarely assign biological functions or cellular functions to an individual molecule — the functions arise from the interaction of all the molecules inhabiting a cellular landscape,” Baumeister says. “That’s where the discovery potential of cryo-ET comes in. Whatever we look at nowadays, there are surprises.”

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"More recently, scientists have moved on to imaging eukaryotic cells — which are palatial in comparison with prokaryotes. This has been possible largely because of the advent of cryo-FIB milling, which allows researchers to slice cells thinly before placing them under an electron microscope. Baumeister and his colleagues used this mash-up of methods to visualize how molecules were arranged in the vicinity of the nucleus in a human cell3 (see ‘Inside scoop’). Their work revealed how previously unseen, nanometre-thin filaments provided structural support to the nucleus — making it one of the stiffest organelles in animal cells."

Comment: Download this article and see the images. It makes sense of my view that life's processes are entirely automatic reactions and decisions, designed by God at life's first appearance.


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