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April 24th 2019

A cell needs to generate forces, for example to move material within the cell or to build complex structures. For this, cells have enzymes that exert a force when they change shape. In this process chemical energy is used. From everyday life we know that the expansion of a compressed gas also yields a force. That is because the entropy (chaos) of the moving gas molecules is increased when they are given more space. The researchers from this programme wanted to find out if a cell could also use this mechanism for force generation.

In 2013, researchers from FOM institute AMOLF, Wageningen University and the Max-Planck-Gesellschaft demonstrated for the first time that protein molecules trapped between long filaments can generate directed forces. Filaments inside a cell are linked to each other by protein linkers, as a result of which the filaments form networks. These networks not only give cells their shape but also move the chromosomes during cell division, for example. The investigated protein linkers move chaotically between the filaments through diffusion.

Force from entropy
The researchers took two filaments linked by protein linkers and sheared the filaments apart from each other to create a configuration in which the linkers within the overlap between the two filaments were very close together. After the experimenter had removed the force that pushed the filaments apart from each other, the filaments were found to move themselves so that their overlap increased. The linkers spread themselves over the growing overlap during this process. The driving force behind this phenomenon is the entropy of the molecules, which increases as the overlap grows. The force generated in this manner was found to be large enough to reverse the filament movement due to the motor enzymes. It is therefore a very relevant force in cells.

The researchers produced a model to gain a better understanding of the force generation mechanism. They discovered that force generation can be explained if the overlap is considered to be a closed space in which proteins move like gas molecules. The forces are correctly predicted by a one dimensional version of the ideal gas law. The linkers moved between filaments by jumping between nearby binding sites. By simulating this movement, the observed rate of filament movement was also explained. Moving filament-linkers therefore provide forces that are analogous to a cylinder with a compressed gas.