Manipulation of Cells and molecules by biomolecular mechanical tweezers

A new type of biomolecular tweezers could help researchers to study how mechanical forces affect the biochemical activity of cells and proteins. The devices, too small to see without a microscope, use opposing magnetic and electrophoretic forces to precisely stretch the cells and molecules, holding them in position so that the activity of receptors and other biochemical activity can be studied.

Arrays of the tweezers could be combined to study multiple molecules and cells simultaneously, providing a high-throughput capability for assessing the effects of mechanical forces on a broad scale.

For example, a cell that's binding the extracellular matrix may bind with one receptor while the matrix is being stretched, and a different receptor when it's not under stress. Those binding differences could drive changes in cell phenotype and affect processes such as cell differentiation. A device like this will allow us to interrogate what the specific binding sites are and what the specific binding triggers are.

Scientists have been able to study how single cells or proteins are affected by mechanical forces, but their activity can vary considerably from cell-to-cell and among molecules. The new tweezers, which are built using nanolithography, can facilitate studying thousands or more cells and proteins in aggregate.

At the center of the tweezers are few micron polystyrene microbeads that contain superparamagnetic nanoparticles. The tiny beads are engineered to adhere to a sample being studied. That sample is attached to a bead on one side, and to a magnetic pad on the other. The magnet draws the bead toward it, while an electrophoretic force created by current flowing through a gold wiring pattern pushes the bead away. The device simultaneously pushes and pulls on the same particle.

Because the forces can be varied, the tweezers can be used to study structures of widely different size scales, from protein molecules to cells. Absolute forces in the nano-Newton range applied by the two sources overcome the much smaller effects of Brownian motion and thermal energy, allowing the tweezers to hold the cells or molecules without constant adjustment.

As a proof of principle for the system, the researchers demonstrated its ability to distinguish between antigen binding to loaded magnetic beads coated with different antibodies. When a sufficient upward force is applied, non-specific antibody coated beads are displaced from the antigen-coated device surface, while beads coated with the specific antibody are more strongly attracted to the surface and retained on it.