Biological complexity: how muscle cells fuse into fibers (Introduction)

by David Turell , Wednesday, May 27, 2020, 00:18 (1642 days ago) @ David Turell

It is an orchestrated dance:

https://phys.org/news/2020-05-urge-merge-cells-fuse.html

"Scientists have known for a decade that cells that fuse with others to perform their essential functions—such as muscle cells that join together to make fibers—form long projections that invade the territory of their fusion partners. But how the thin and floppy polymers involved in this process propel mechanically stiff protrusions has been unknown.

"In a new study published online today in Nature Cell Biology, UT Southwestern scientists outline the mechanisms behind the formation of these projections, focusing on the interaction between two proteins known as actin and dynamin. The findings, they say, offer insight on a key cellular process that's essential for the conception, development, regeneration, and physiology of multicellular organisms

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"First, adhesion molecules draw cell membranes together, but leave a gap between cells; next, one cell extends fingerlike projections that invade the other cell; finally, so-called fusogenic proteins bring the cells' membranes even closer to touch and merge.

"For that middle step, Chen says, research from her lab and others has shown that a protein called actin plays a key role in forming projections. However, actin forms floppy and thin polymers, known as actin filaments, each with a diameter of only 7 nanometers. How these thin filaments become mechanically rigid enough to push out projections that invade other cells was unclear.

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"To solve it, Chen and her colleagues studied actin's interaction with dynamin, a protein that can release energy from specific chemical bonds found throughout cells. One of dynamin's roles is to pinch off newly formed vesicles that bring cargo into cells, by forming a structure around the "neck" of the vesicles protruding in from the cell membrane. Although previous studies have shown that dynamin and actin were associated with each other in many cellular structures, how they work together has remained a mystery for two decades.

"Using fruit fly muscle cells as a model system, Chen and her team started by observing muscle cell fusion in embryos genetically engineered to not make any functional dynamin. They found that without dynamin function, not only could these cells no longer merge, they also couldn't form the normal projections, suggesting that dynamin plays a key role in this step of the process.

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"Although this experiment shows that dynamin has the capacity to capture and hold multiple actin filaments into stronger bundles, Chen says, fully occupied dynamin helices are unlikely to last long in cells, where ample energy sources that can cause these dynamin structures to dissolve into individual units is abundant. Sure enough, when the researchers added energy sources to the dynamin-actin mix, the dynamin helices did come apart, but not in a synchronized fashion. While fully assembled helices broke apart, others remained—keeping the actin bundles together while allowing new filaments to emanate from areas unbound by dynamin. Such a dynamic process ultimately leads to the formation of multiple interconnected parallel actin bundles, hence further increasing the mechanical strength of the actin network, says Chen. Experiments in cells showed that the dynamic actin bundling process was critical for cells to form projections and fuse with other cells."

Comment: this type of cellular coordination is designed into the cells various activities as the embryo is formed. Not learned cooperation, but designed cooperation. If cells had to learn how to do this, no embryo would ever form.