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Strong in the right place and time

Strong in the right place and time

Researchers from TU Delft and the NWO Institute AMOLF have discovered how certain molecular bonds make living cells flexible to move and strong to withstand forces. Paradoxically, this power turns out to be sensitive Catch the bond They are usually weak and inactive, but travel to specific places where and when cells are damaged. The discovery was published today in Nature Materials.

Molecular bond proteins are found in many different tissues, both within and between cells. These bonds break up regularly, as do most biological bonds, but they have a peculiar property: If you pull the fishing bond too hard, it actually starts to bond more tightly. The researchers found that this ability strengthens the material in specific places where the bond is subjected to stress. This discovery is a breakthrough, 20 years after the first discovery of such links. This is also the first time researchers have seen fishing links work together in biological materials.

Both are flexible and strong
Former AMOLF researcher Yuval Malla explains: “We usually define how strong something is in two ways: the material can either deform well – stretch very far without breaking, like rubber – or the material can withstand a great deal of force, for example bricks; Although the material is strong, it can stretch a bit before breaking.When studying the nature of fishing bonds, we found that these molecular bonds were able to do both: being flexible and strong, despite their weak molecular bonds.Then we thought: Does gripping the bonds explain why living cells combine the flexibility of rubber with the strength of bricks?”

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To test these ideas, the researchers measured the mechanical properties of a cytoskeletal network that they reconstructed in the lab, in collaboration with a biophysics group, to pull out individual bonds. They found that many bonds float, shorten, and then release. However, when the researchers deformed the material, they found that many links travel to specially damaged sites in order to bond. According to Al-Mulla, they do so “because fishing ties accumulate weaknesses wherever and whenever they are needed to make the network very strong.”

related to diseases
The study involved a modified version of the same protein, which is known to occur in an inherited disease that leads to kidney failure. Contrary to common fishing links, the researchers found that this modified version was always active. This greater binding force makes it more difficult for the mutant to move, but also paradoxically makes the network weaker because the bonds don’t build up when necessary, says group leader Gypsy Koenderink: “By understanding the mutated protein better, we can also, in the future, understand the process of kidney failure.” Additionally, we hope to understand how catch bonds play a role in the extent of cancer cell spread.”

physical view of life
The research group of TU Delft Professor Gijsje Koenderink is mainly concerned with the physical properties of living matter. The main theme in her collection is that living cells and tissues must be dynamic and flexible, but also robust: “This property is different from all synthetic materials that we know of,” says Koenderink. “Our ambition is to learn new design principles from living materials to create synthetic materials that can be both flexible and strong. In fact, we are currently working with chemists and biophysicists like Sander Tans at AMOLF to try to create these synthetic fishing bonds.”

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