by Andre on 5 September 2009
If you cut yourself, a blood clot can save your life: platelets aggregate and fibrin fibers form a mesh that catches red cells and prevents you from bleeding out. If you have heart problems, a clot can also take your life: heart attacks are often the result of clots in the coronary artery. Just such a clot is shown below. This is a colorized electron microscope image of a thrombus that was removed from a heart attack patient. You can see the mesh of straight fibrin fibers in brown, activated platelets in gray, red cells in red, and a leukocyte in green.
To do their job effectively, blood clots must have an open structure so that enzymes can diffuse in to break the clot down when it is no longer needed. This can be achieved with a stiff scaffold with lots of spaces between the structural elements. A scaffold of stiff structural elements would normally be stiff itself and probably also quite brittle, but one of the first things you’ll notice if you take a blood clot in your fingers is that it’s squishy and stretchy, something like a water-logged rubber (or hydrogel). The thing is, rubber is made of highly flexible, thermally oscillating chains that provide extensibility but they have very small pores that wouldn’t allow enzymes to diffuse through effectively. So how does fibrin balance the large pore sizes with high extensibility?
We argue in our paper in Science that protein unfolding gives fibrin’s stiff fibers an intrinsic extensibility. In other words, it is the unravelling of compact protein structures, possibly fibrin’s coiled-coils, that allow blood clots to stretch so far. We hypothesized that this would be the case when we published our single molecule study of fibrinogen mechanics a couple of years ago, but to nail it down, we had to look at several structural levels from the macroscopic (centimeter level), through the microscopic network structure, to the nanometer molecular level.
It seems then that fibrin has evolved a molecular structure that enables it to play its amazing role. It self-assembles in clots into an open network that stops blood flow but can also be broken down and avoids being brittle by having structural elements that unfold under force. It’s an amazing material, and you make it and break it all the time.