Researchers from TU Delft and NWO Institute AMOLF discovered how certain molecular bonds make living cells both flexible to move and strong to withstand forces. Paradoxically, it turns out that this force-sensitive catch bonds are usually weak and inactive, but travel to specific places where and when cells become damaged. This discovery was published today in Nature Materials.
Molecular catch bond proteins are found in many different tissues, both within and between cells. These bonds fall apart regularly, as most biological bonds do, but they have a peculiar property: if you pull hard on a catch bond, it actually starts to bind tighter. Researchers found that this ability strengthens the material in specific places where the bond experiences tension. The discovery is a breakthrough, 20 years after the first discovery of such bonds. This is also the first time the researchers have witnessed catch bonds working together in biological materials.
Both flexible and strong
Former AMOLF researcher Yuval Mulla explains: “Usually we define how strong something is in two ways: a material can either deform well – stretch very far without breaking, like rubber – or the material can bear a lot of force, for example a brick; although the material is strong, it can only stretch a little bit before breaking. In studying the nature of catch bonds, we found that these molecular bonds were able to do both: be flexible and strong, even though their molecular bonds are weak. And then we thought: would catch bonds explain why living cells combine the elasticity of rubber with the strength of a brick?”
To test these ideas, the researchers measured the mechanical properties of the cytoskeleton network that they reconstructed in the lab, in collaboration with the Biophysics group, to pull single bonds. They found that many of the bonds just float around, shorten and then release. However, when the researchers deformed the material, they found that many bonds travel to especially damaged sites to bond. According to Mulla, they do this “because the catch bonds accumulate in weak spots where and when they are needed to make the network very strong.”
Linked to diseases
The study involved a mutated version of the same protein, which is known to occur in a genetic disease that leads to kidney failure. Unlike a common catch bond, the researchers found that this mutated version was always active. This greater binding force makes it difficult for the mutant to move, but paradoxically also makes the network weaker because the bonds do not accumulate where necessary, says group leader Gijsje Koenderink: “By better understanding the mutated protein, we can in the future perhaps also understand the process of kidney failure. In addition, we hope to understand how catch bonds play a role in how invasive cancer cells are.”
Material view of life
The research group of TU Delft professor Gijsje Koenderink is mainly interested in material properties of living matter. A central theme in her group is that living cells and tissues must be dynamic and flexible, but also strong: “This property is different from all synthetic materials we know,” says Koenderink. “Our ambition is to learn new design principles from living materials to create synthetic materials that can be flexible and strong at the same time. In fact, we are currently working with chemists and biophysicists like Sander Tans at AMOLF to try to create such synthetic catch bonds.”