Final Activity Report Summary - CAGING BIOPOLYMERS (Statistical mechanics of biomolecular confinement and translocation)
Biopolymers have reached a high level of complexity through the selection pressure of evolution. The large variety of genetic material present in living organism is a reflection of the numerous molecular processes that occur in every living organism. A large amount of energy is spent just to keep every element at the best working condition. Most of the activity in the cell is regulated by molecules called proteins; this includes the task of repairing and cleaning other proteins. One of the major pitfalls of a protein based system is that such molecules can get stuck in the wrong shape while they self-assemble. Most of the time a "broken" protein does not cause any damage and they are simply destroyed after a few hours. However sometimes the cell is not so lucky and the malfunctioning protein causes cell death, when this happens on a large scale it induces diseases such as Alzheimer. In order not to get extinct all living organisms developed protections against this threat. In our work we focused on a particular class of repairing machinery called chaperonins. Their function is to capture and repair broken proteins. Once the protein is captured it is then confined in a molecular prison. Inside the chaperonin the protein is forced through several repairing cycles.
In our work we tried to understand the physics of this machinery. We started with a rather simple idea, consisting in reducing the chaperonin to a simple cage with the only function of restricting the movement of the protein. If a hole is created in the chamber, the trapped protein will try to escape squeezing itself out like toothpaste. We discovered that this is a very efficient way to repair proteins because it forces them out of the local structure in which they got stuck giving them another chance to reach the correct structure. In addition this is a very natural way or treating proteins, because extrusions are very frequent in other biomolecular processes, the most important of which is the synthesis of the protein itself , where the new born protein comes out a piece at the time like the tape of the telegraph. We then went back to real chaperonin to understand how this extrusion could take place. At the centre of the molecule there is a restriction filled with flexible chains.
Our project consisted in characterising the properties of this region. We moved in two parallel directions. The first was aimed at the general understanding of physical properties of polymers grafted surfaces with different chemical composition and curvature. We started by considering a flat surface with mono- and bi-disperse polymers. We then found that there was a regime defined by the grafting densities and polymer length were the brush started to become stretched. In other words, to stretch the polymers on the surface, you can squeeze a lot of them like in a brush or take fewer but make them much longer. The applications to surface science are numerous because the end point of each grafted polymer is chemically active and effective only if exposed to the solvent. The second research direction pointed at a detailed understanding of the influence of the flexible chains in the equatorial region, over the extrusion process. We carried out extensive computer simulations and we observed a small protein going through fairly easily. The results not only gave strong evidence that extrusion could take place in the chaperonin, but also it sketches the building blocks of an artificial protein repairing machine: cages, hole, filter flexible chains in the middle.
In our work we tried to understand the physics of this machinery. We started with a rather simple idea, consisting in reducing the chaperonin to a simple cage with the only function of restricting the movement of the protein. If a hole is created in the chamber, the trapped protein will try to escape squeezing itself out like toothpaste. We discovered that this is a very efficient way to repair proteins because it forces them out of the local structure in which they got stuck giving them another chance to reach the correct structure. In addition this is a very natural way or treating proteins, because extrusions are very frequent in other biomolecular processes, the most important of which is the synthesis of the protein itself , where the new born protein comes out a piece at the time like the tape of the telegraph. We then went back to real chaperonin to understand how this extrusion could take place. At the centre of the molecule there is a restriction filled with flexible chains.
Our project consisted in characterising the properties of this region. We moved in two parallel directions. The first was aimed at the general understanding of physical properties of polymers grafted surfaces with different chemical composition and curvature. We started by considering a flat surface with mono- and bi-disperse polymers. We then found that there was a regime defined by the grafting densities and polymer length were the brush started to become stretched. In other words, to stretch the polymers on the surface, you can squeeze a lot of them like in a brush or take fewer but make them much longer. The applications to surface science are numerous because the end point of each grafted polymer is chemically active and effective only if exposed to the solvent. The second research direction pointed at a detailed understanding of the influence of the flexible chains in the equatorial region, over the extrusion process. We carried out extensive computer simulations and we observed a small protein going through fairly easily. The results not only gave strong evidence that extrusion could take place in the chaperonin, but also it sketches the building blocks of an artificial protein repairing machine: cages, hole, filter flexible chains in the middle.