Holding on to cells with DNA

Mammalian cells need something to hold on to before they can stick to each other and form tissues. The plastic dishes that cells grow on in the lab need to be first coated with special chemicals that grab the cells and convince them to stick. Once the first batch of cells is down they start forming their own matrix of proteins and fibers that can grab new cells as they are formed, slowly creating a dense layer of cells. Tissue engineering aims to make three dimensional, biodegradable scaffolds that cultured cells can grow on to form body parts, like the ear-shaped bit of cow cartilage that was transplanted onto the back of a mouse back in 1995.

Having versatile scaffolds that can have multiple chemical signals for different types of cells in different shapes and different densities is important for creating more complex tissues and organs and many researchers are working on new and exciting designs. One particularly exciting set of experiments comes from my colleague Faisal Aldaye who is translating his expertise in DNA nanotechnology to new scaffolds for tissue engineering. DNA is a double helix, and how each side pairs together depends on the sequence of the strand. By carefully designing short sequences of DNA that bind to each other in new and clever geometries all sorts of shapes can be made.

Faisal designed pieces of DNA that self-assemble into thick long strands four double helices across that structurally resemble the protein fibers of the natural extracellular matrix. Cells don't naturally bind to DNA strands, so an extra strand that studs the fiber allows for binding of proteins and chemical markers that signal for the cells to stick. After showing that cells will bind to chemically decorated DNA, Faisal then tuned the flexibility of the scaffold fiber by adding stretches of DNA strands that don't bind to anything, leaving just the much bendier single-stranded DNA to flop around. Stiff scaffolds hold the cells taut in a thin layer, while flexible scaffolds can be bent by the cells themselves, which ball up into smaller, rounder cells when grown on DNA with longer single stranded segments.

DNA nanotechnology is a fun way to think about DNA not as the genetic code but as a powerful biological building material. Go check out the paper, hot off the presses! Aldaye et. al. "A Structurally Tunable DNA-Based Extracellular Matrix" in the Journal of the American Chemical Society.