A microscale force technique for cellular mechanobiology and nuclear mechanics
The magnetic tweezers device built in our lab enables the manipulation of cells and molecules through the application of controlled mechanical forces (from a few pN to several nN) to micron-sized magnetic beads bound to the biological entity of interest.
The working principle of this biophysical technique relies on the force generated by a simple electromagnet. An electrical current passing through a solenoid enclosing a ferromagnetic needle generates a magnetic field gradient that pulls magnetic beads towards the source of the field and to the tip of the electromagnetic core/needle. The current is controlled though a LabVIEW interface. The positioning of the tweezers is further controlled by a micromanipulator that allows translational movement across all three axes with nanometer precision. The force exerted on the cell-bound bead is critically dependent on the current and the distance between the tip of the needle and the bead. A particle-tracking algorithm is used for the calibration of the magnetic tweezer.
Applications of magnetic tweezers
The magnetic tweezers provide quantitative data on the local properties of living adherent cells (e.g. elasticity and viscosity). This data can be utilised to investigate a number of different aspects of cell biomechanics.
Force transduction away from the surface
Mechanotransduction (how cells translate mechanical cues to biochemical signals) may not be merely restricted to cell surface receptors and adhesions.
Recent studies have fuelled the speculation that the nucleus itself may also act as a cellular mechanosensor that can potentially directly modulate expression of mechanosensitive genes. With the magnetic tweezers we have the option of manipulating isolated nuclei from cells. This will pave the way for a better understanding of force transmission into the nucleus and the molecular mechanisms mediating nuclear mechanotransduction.
Force application with the magnetic tweezers can also be combined with fluorescent microscopy and FRET (Forster Energy Resonance Transfer) to capture rapid mechanochemical signaling activities in living cells.