Magnetic tweezers

Most commonly magnetic tweezers are used to study mechanical properties of biological macromolecules like DNA or proteins in single-molecule experiments.

Irregular shaped particles present a larger surface and hence a higher probability to bind to the molecules to be studied.

Theoretically it would be possible to calculate the force on the beads with these formulae; however the results are not very reliable due to uncertainties of the involved variables, but they allow estimating the order of magnitude and help to better understand the system.

[3] The use of ferromagnetic nanowires for the operation of magnetic tweezers enlarges their experimental application range.

It is possible to produce nanowires with surface segments that present different chemical properties, which allows controlling the position where the studied molecules can bind to the wire.

Since this scale is rather large in comparison to the distances, when the microbead moves in an experiment, the force acting on it may be treated as constant.

In order to increase the maximum field strength, a core of a soft paramagnetic material with high saturation and low remanence may be added to the solenoid.

Additionally, using electromagnets requires high currents that produce heat that may necessitate a cooling system.

[1] The displacement of the magnetic beads corresponds to the response of the system to the imposed magnetic field and hence needs to be precisely measured: In a typical set-up, the experimental volume is illuminated from the top so that the beads produce diffraction rings in the focal plane of an objective which is placed under the tethering surface.

These calibration images are obtained by keeping a bead fixed while displacing the objective, i.e. the focal plane, with the help of piezoelectric elements by known distances.

[6] The obtained coordinates may be used as input for a digital feedback loop that controls the magnetic field strength, for example, in order to keep the bead at a certain position.

The determination of the force that is exerted by the magnetic field on the magnetic beads can be calculated considering thermal fluctuations of the bead in the horizontal plane: The problem is rotational symmetric with respect to the vertical axis; hereafter one arbitrarily picked direction in the symmetry plane is called

Considering only absolute values of the involved vectors it is geometrically clear that the proportionality constant is the force exerted by the magnets

For more accurate results, one may subtract the effect due to finite camera integration time from the experimental spectrum before doing the fit.

[9] Applying magnetic theory to the study of biology is a biophysical technique that started to appear in Germany in the early 1920s.

[11] In 1949 at Cambridge University, Francis Crick and Arthur Hughes demonstrated a novel use of the technique, calling it "The Magnetic Particle Method."

[12] Although some of their methods and measurements were self-admittedly crude, their work demonstrated the usefulness of magnetic field particle manipulation and paved the way for further developments of this technique.

The magnetic particle phagocytosis method continued to be used for many years to research cytoplasm rheology and other physical properties in whole cells.

Since 2002, the potential for experiments involving many tethering molecules and parallel magnetic beads has been explored, shedding light on interaction mechanics, especially in the case of DNA-binding proteins.

[17] A technique was published in 2005 that involved coating a magnetic bead with a molecular receptor and the glass slide with its ligand.

The technique involves attaching beads to the extracellular matrix and manipulating the cell from the outside of the membrane to look at structural elasticity.

[20] Magnetic tweezers can be used to measure mechanical properties such as rheology, the study of matter flow and elasticity, in whole cells.

Measuring the movement of the beads inside the cell in response to manipulation from the external magnetic field yields information on the physical environment inside the cell and internal media rheology: viscosity of the cytoplasm, rigidity of internal structure, and ease of particle flow.

[11] The schematic shown at right depicts the experimental setup devised by Bonakdar and Schilling, et al. (2015)[19] for studying the structural protein plectin in mouse cells.

Through the single-molecule method, molecular tweezers provide a close look into the physical and mechanical properties of biological macromolecules.

This has allowed recent advances in understanding more about DNA-binding proteins, receptor-ligand interactions,[18] and restriction enzyme cleavage.

[20] This is also similar to the method of pulling apart receptor-ligand interactions with magnetic tweezers to measure dissociation force.

Optical tweezers have the problem that the laser beam may also interact with other particles of the biological sample due to contrasts in the refractive index.

Thanks to the low trap stiffness, the range of forces accessible with magnetic tweezers is lower in comparison with the two other techniques.

An important drawback of magnetic tweezers is the low temporal and spatial resolution due to the data acquisition via video-microscopy.