Northwestern University’s Nanocombinatorics Facilitates Stem Cell Differentiation

A research team led by Chad A. Mirkin from the Northwestern University has devised a powerful analytical technique called nanocombinatorics to rapidly detect the physical and chemical structures that can influence stem cells to turn into mature bone cells called osteocytes.

Nanocombinatorics holds promise for researchers focusing on nanotechnology, materials engineering and chemistry fields to evaluate the best physical or chemical structures needed for a specific function or process. It finds applications in detecting active molecules for discovering drugs, knowing properties resulted by nanostructures, monitoring catalysts for energy conversion and improving materials for tissue regeneration.

Nanocombinatorics uses polymer pen lithography technique, a method developed at the Northwestern University. In this technique, a rubber stamp comprising nearly 11 million sharp pyramids or polymeric pens is placed over a transparent glass backing and is accurately controlled by an atomic force microscope to produce preferred patterns over a surface. Molecules are applied over each pyramid for a specific purpose.

In this work, the research team utilized molecules that are capable of binding to proteins such as fibronectin. The team then quickly formed millions of textured features on a large area called a library. The library comprised nearly 10,000 fibronectin patterns, which have nearly 25 million features, with sizes ranging between a few hundred nanometers to a number of micrometers. The team then brought in mesenchymal stem cells to the library comprising millions of fibronectin features. What the team discovered was areas with and without stem cell differentiation. Nanoscale features, especially 300-nm-diameter protein spots were more likely to become bone-like cells when compared to micron-scale features.

The team then created a library comprising only 300-nm dots and brought in stem cells. Here, nearly all cells turned into bone-like cells. This technique did not utilize any additional chemical cues to achieve stem cell differentiation and the patterned structures’ physical cues were the sole dictator for converting stem cells into osteocytes, thus controlling stem cell differentiation effectively when compared to existing chemical reagent methods.

The Proceedings of the National Academy of Sciences have reported the details of the technique and proof of concept.