Discovery of novel drug candidates boosted by new tunable gels

A team led by CUNY ASRC Nanoscience Initiative Director Rein V. Ulijn and Professor Mathew Dalby of the University of Glasgow has developed gels with tunable properties that mimic the nanofibrous structure and mechanical properties of biological tissue. These gels can be used to monitor stem cell differentiation and allow for the identification of molecules involved in differentiation, as reported in the latest issue of Chem, to be published on August 11.

The study—a culmination of five years worth of research and which also features work by Nanoscience Initiative postdoctoral associate Ayala Lampel—shows how new biomaterials can enable identification of cell guiding metabolites as potential drug candidates, taking the guesswork out of identifying factors that drive stem cell differentiation.

“My lab is focused on repurposing biomolecules, such as peptides, for fabrication of functional materials. In this work we developed peptide gels that provide nanofiber morphology and as-simple-as-possible chemistry with tunable stiffness to serve as a blank-slate background for cell culture. These gels could be used to observe changes in stem cell metabolism during differentiation,” Ulijn said.

Ulijn developed the gels on the basis of combining small building-block molecules that spontaneously form a network of nanosized fibers that are coated with simple, cell compatible chemical groups. The nanofiber network density could be tuned to adjust the stiffness of the resulting gel. These gels were ideally suited for Dalby’s purposes whose group is interested in elucidating the physical factors that influence stem cell differentiation.

“Matt and his team performed metabolomics analysis to find out how the key metabolites within a stem cell are used up during the differentiation process,” Ulijn said. “The really clever part is that they subsequently used those identified simple lipids to direct differentiation in ways that are much simpler compared to currently used methods.”

“That you can use simple metabolites like cholesterol sulfate, which is readily available, to induce differentiation is in my view very powerful if you think about this as a potential drug candidate,” Ulijn added. “These metabolites are inherently biocompatible, so the hurdles to approval are going to be much lower compared to those associated with completely new chemical entities.”

This work was funded by the UK Biotechnology and Biological Sciences Research Council with additional support from the UK Engineering and Physical Sciences Research Council, the California Institute for Regenerative Medicine, the British Heart Foundation, the PBC Foundation, and the Israeli Council for Higher Education.

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About the ASRC: The CUNY Advanced Science Research Center (ASRC) is a University-wide venture that elevates CUNY’s legacy of scientific research and education through initiatives in five distinctive, but increasingly interconnected disciplines: Nanoscience, Photonics, Structural Biology, Neuroscience and Environmental Sciences. Led by Dr. Gillian Small, Vice Chancellor for Research and the ASRC’s executive director, the center is designed to promote a unique, interdisciplinary research culture. Researchers from each of the initiatives work side by side in the ASRC’s core facilities, sharing equipment that is among the most advanced available. Funding for the ASRC from New York State is gratefully acknowledged.