“Patch” Directs Stem Cells to Differentiate

Researchers from North Carolina State and Duke University have developed a nanoscale “patch” that can direct a stem cell to differentiate into a bone cell or a cartilage cell. The patches sensitize targeted cell receptors to make them more responsive to the signals that control cell activity.

Cells in a living organism communicate by physical contact. When receptors on the surface of a cell are triggered by target molecules, called ligands, the cell receives instructions to changes its behavior in some way. According to the researchers, ligands must be present in certain concentrations to trigger the receptors. If there are not enough target ligands, the receptors will not respond.

To solve that problem they developed the patches and embedded them with tiny protein fragments, called peptides. These peptides bond to a specific cell receptor, making it more sensitive to its target ligand. The result is it takes fewer ligand molecules to trigger the receptor and its resulting behavior modification.

“This study shows that our concept can work, and there are a host of potential applications, ” says Thom LaBean, Ph.D., an associate professor of materials science at North Carolina State and senior author of a paper describing the work. “For example, if we identify the relevant peptides, we could create patches that sensitize cells to promote cartilage growth on one side of the patch and bone growth on the other side. This could be used to expedite healing or to enable tissue engineering of biomedical implants.”

The patch itself is made of DNA that researchers have programmed to self-assemble into flexible, two-dimensional sheets. The sheets incorporate molecules called biotin and streptavidin which hold and organize the peptides that are used to sensitize cell receptors.

“These peptides can bind with cell receptors and sensitize them, without blocking the interaction between the receptors and their target ligands, ” said Ronnie Pedersen a Ph.D. student at Duke University and lead author of the paper. “That’s what makes this approach work.” The paper, “Sensitization of Transforming Growth Factor-ß Signaling by Multiple Peptides Patterned on DNA Nanostructures, ” was published online November 8 in the journal Biomacromolecules.