Self-Assembling Molecule Nurtures Stem Cells

Our cells live in a carbohydrate jungle. In particular, stem cells interact with a forest full of sugars, which trigger how they grow and differentiate. But when scientists grow stem cells in the lab, the culture medium provides a vastly different environment. To replicate the cells’ native surroundings, researchers constructed a sugar-decorated molecule that self-assembles into a hydrogel that mimics the extracellular matrix (Bioconjugate Chem. 2014, DOI: 10.1021/bc500187m). The gel encourages mouse embryonic stem cells to grow and zygotes to develop into blastocysts, suggesting the molecule someday could help grow human tissue in the lab, the researcher say.

The extracellular matrix that cells sit in is a complex mixture of proteins and sugar molecules. Molecules on the surface of stem cells, often sugars themselves, interact with this matrix in ways that are critical to stem cell differentiation and development, says Bing Xu of Brandeis University.

For more than a decade, Xu has been developing supramolecular assemblies, molecules that bind together to create materials with new and desirable properties. Xu hypothesized that a supramolecular assembly generated from a glycoconjugate—a carbohydrate molecule covalently linked to other molecules—might recreate the molecular environment of the extracellular matrix and facilitate stem cell growth.

To create the glycoconjugate, the researchers stitched together a sugar called glucosamine, the nucleobase adenine, and a string of four amino acids. To help encourage interactions between the molecule and cells, they chose an amino-acid sequence known to interact with integrins, proteins that coat the surface of stem cells and coordinate cell-to-cell interactions. The team decided to include adenine because previous work showed that the nucleobase promotes self-assembly. Using static light scattering, the researchers studied gels formed by different concentrations of the glycoconjugate in buffer and found that the assembly formed nanofibers and clusters of particles with structures that slightly resembled that of amyloid fibrils, Xu says.

Xu’s team grew mouse embryonic stem cells on media containing the glycoconjugate gel. After 48 hours, they counted twice as many cells in the culture with 200 μM glycoconjugate than in a culture without it. In another experiment, the researchers found that 84% of mouse zygotes grown in 500 μM glycoconjugate developed into blastocysts after four days compared to 31% in a glycoconjugate-free growth medium.

The researchers next want to understand how the glycoconjugate promotes stem cell growth, in particular which proteins are involved.

The ability of these supramolecular assemblies to trigger activity in stem cells is exciting, says Brian K. Shoichet of the University of California, San Francisco. “People should be aware of this work.” He wonders whether it would be possible to tweak the design of the self-assembling molecules to direct stem cells to differentiate in a particular way.