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Figure 1. Scheme of the micromechanical experiments. Magnetic poles (6 µm wide, 20 µm separation) generate a force on a paramagnetic bead positioned in the nucleus of a HeLa cell. Electric coils allow the control of amplitude and direction of the force. Magnetic yoke and electric coils are not to scale.
Detailed knowledge about spatial organization in a living cell is crucial to the understanding of the molecular processes that govern cell function. A striking example is the regulation of gene expression. For example, we cannot understand the orchestrated activity – and the silencing – of many thousands of genes in any given cell just on the basis of DNA sequences. There is strong evidence that gene expression is also controlled by the spatial organization of the DNA (packed together with proteins in a structure called chromatin) in the nucleus. This has inspired many studies on the mechanical properties of DNA and chromatin. However, so far these studies have been limited exclusively to isolated chromosomes. With the new method developed at the Biophysical Engineering group, it is now possible to address the mechanical properties of chromatin and the internal structure of the nucleus inside a living cell.
The principle of the device is shown is figure 1. A small magnetic bead (1 mm diameter) is injected into the nucleus of a living cell using a micropipette. Three external magnetic poles are positioned around the cell and are used to generate a magnetic force on the magnetic bead into the direction of one of the poles depending on the currents through the coils. The displacement of the bead inside the nucleus in response to the force on the bead strongly depends on the mechanical properties of the chromatin inside the nucleus. The nanometer displacements of the beads are measured by video microscopy. In this way it was possible to obtain parameters like the elasticity and viscosity of chromatin. Using an intuitive polymer model for the chromatin structure, these data predict an organization of chromatin in domains which do not completely fill the nucleus, in excellent agreement with the current understanding of chromatin organization.
The long-term goal is to develop and exploit magnetic nanodevices that can be implanted inside the living cell and can be used as biosensors to monitor local chemical and physical processes in cells and tissues. It may also be possible to mechanically or chemically interfere with cellular processes in a highly specific manner.
