Biochemistry: Biomolecular Tweezers for Studying Cells

03/12/2014

Researchers from Georgia Tech and Emory University have developed a new type of biomolecular tweezers that could help researchers 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.

“Our lab has been very interested in mechanical-chemical switches in the extracellular matrix, but we currently have a difficult time interrogating these mechanisms and discovering how they work in vivo,” said Thomas Barker, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “This device could help biologists and biomedical engineers answer questions that cannot be answered right now.”

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. But they are now difficult to study.

“Having a device like this will allow us to interrogate what the specific binding sites are and what the specific binding triggers are,” Barker explained. “Right now, we know very little about this area when it comes to protein biochemistry.”

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. The researchers are currently testing prototype 15 by 15 arrays which they believe could be scaled up.

“For me, it’s not sufficient to pull and hold onto a single protein,” said Barker. “I have to pull and hold onto tens of thousands of proteins to really use the technologies we have to develop molecular probes.”

At the center of the tweezers are 2.8- 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.

COMPAMED.de; Source: Georgia Tech and Emory University