Abstract

Cancelled - 3D Environments to Model Cell-Matrix Interactions Important in Development and Disease

Cathy Merry, Associate Professor of Stem Cell Glycobiology, University of Nottingham

The pericellular zone provides a dynamic, highly interactive interface between cells and their local microenvironment. Within this zone, complex sugars – glycosaminoglycans (GAGs) have multiple functions, stabilising growth factor-receptor complexes, enabling efficient multimerisation of cytokine subunits and increasing the local concentration of soluble factors close to the cell surface. The structural heterogeneity that underpins the ability of GAGs to interact selectively with multiple ligands has previously hindered their analysis. Built via non-template driven synthesis in the Golgi, hard to sequence and technically challenging to synthesise, deep understanding of the role of GAGs in stem cell biology has remained elusive, with many groups in research and industrial settings using materials of limited biological relevance. Often, the 3D matrix of choice for groups wishing to model cell-matrix interactions is Matrigel, a product prepared from a mouse tumour cell line. Informative though those studies have been, they have masked the delicate balance of interacting signalling pathways regulated by in vivo relevant GAGs. Similarly, if we wish to use technologies such as induced pluripotent stem cells and gene editing to model matrix-related diseases we need to develop much more defined in vitro test environments in which we can closely control and analyse the protein and carbohydrate components laid down by these cells. Coming from a strong background in GAG biochemistry, we have developed methods for functionalisation of biomaterials to display selected GAGs in 3D environments suitable for the culture and directed differentiation of stem cells.