Biological complexity: mechanical forces in cells (2) (Introduction)

by David Turell , Wednesday, February 15, 2017, 19:59 (2838 days ago) @ David Turell

Another set of discoveries on mechanical forces that control epithelial cell reproduction to help maintain proper cell numbers in covering sheets of tissue:

https://www.sciencedaily.com/releases/2017/02/170215131543.htm

"Research published in Nature from scientists at Huntsman Cancer Institute (HCI) at the University of Utah shows how epithelial cells naturally turn over, maintaining constant numbers between cell division and cell death.

"Epithelial cells comprise the skin and skin-like linings that coat internal organs, giving organs a protective barrier so they can function properly. Cells turn over very quickly in epithelia. To maintain healthy cell densities, an equal number of cells must divide and die. If that balance gets thrown off, inflammatory diseases or cancers can arise.

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"'If too many epithelial cells die, you can lose the organ barrier function and inflammatory diseases like asthma and colitis can result. On the other hand, if too many cells divide compared to the number dying, this can cause an overabundance of cells, which can lead to tumor formation. So imbalance on either side is problematic."

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"'We knew there had to be some kind of regulation to tie the death and division processes together," says Rosenblatt. "What we found boils down to really simple principles. It's all mechanical tension. If the cells get too crowded -- 1.6-fold more crowded -- then they pop some cells out that later die. The extrusion of cells enables the cell sheets to return to densities they like."

"On the flip side, researchers noticed that cells divided in sparser areas. They realized those sparse regions were creating a tension on the cells to stretch.
"If the cells become too sparse, then they activate cells to divide -- and that signal to divide comes from mechanical stretch," explains Rosenblatt. "To test this, we stretched cells and found that stretch could trigger cells to divide within only one hour! The process also showed us that stretch is a normal trigger for cell division."

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"The next question was figuring out what caused these processes to happen. Rosenblatt's team discovered both cell division and death were controlled by the same protein, Piezo1.

"'Basically this same protein is sensing both crowding and stretch -- but the outcome is very different, depending on what state the cells are in," says Rosenblatt. "Piezo1 is sort of like a thermostat, regulating two different sides. Just like a thermostat regulates both heat and cold, it makes sense to have one sensor measuring crowding and stretch. If there were two separate regulators, things could get out of hand fairly quickly if one sensor breaks."

"In addition to understanding how Piezo1 is involved in regulation, Rosenblatt's team also identified a stage in the cell cycle where cells sit paused for repair.

"'We had always assumed that once cells start a division cycle, they just power through. We didn't know that they take breaks throughout the cell cycle," explains Rosenblatt. "But we found a point where the cells were just stalled, waiting to divide. A lot of things need to happen for cells to divide. The DNA needs to replicate so it can divide in half, providing each new cell with the same DNA as the parent. These cells have everything ready to do that, but they still pause there at a step that we did not expect to be regulated. Cells could be paused waiting to reach a certain size. Once they reach this size, stretch triggers them to divide.'"

Comment: Again is this example mechanical forces are carefully regulating how cells reproduce. In most soft tissues cells are turning over to new cells constantly. Obviously bone is different, and turnover is not as fast in the brain where neurons are more fixed. It is interesting how many controls are outside DNA control. Biologic complexity is great design!