Understanding Magnetic Tweezers: Applicability And Utility In Single Molecule Microscopy

Magnetic tweezer instrumentation grants the ability to apply force and torque to a single molecule, as well as the ability to observe the molecule’s response to that force and torque. Magnetic tweezer experiments often seek to measure changes in the extension or relaxation of a polymer, a functionality useful, for example, in exploring how different enzymes manipulate polymer structures.
Prof. Maria Mills, Ph.D., along with her team of researchers at the University of Missouri (Mizzou), applies a novel “combination of force, torque, and fluorescence to understand how proteins remodel the structure of DNA. The group uses magnetic tweezers to pull on and twist individual DNA molecules and observe protein-induced changes in the DNA structure.” This article examines magnetic tweezer capabilities and limitations, with a focus on the instrument’s application in Prof. Mills’ research.
To accomplish both pulling and twisting — the latter a capability unique to magnetic tweezers — the instrument uses its namesake magnets to manipulate magnetic beads within the apparatus. The beads are attached to the polymer of interest so, when the magnetic field is rotated by turning the magnets with a stepper motor, the beads rotate, twisting the polymer. Users can precisely control the speed and degree of rotation.
The Mizzou team’s apparatus uses a Mad City Labs instrument to move the magnets (hence, moving the beads), allowing the researchers to vary pulling force over a range between fractions of a piconewton (10-12 newtons) and up to about 19 piconewtons (pN). By combining the basic magnetic tweezer setup with fluorescence microscopy, users can create an inverted microscope with the sample-manipulation properties of magnetic tweezers — a unique instrument that can detect fluorescently labeled molecules and apply force at the same time.