Spatially controlled glycocalyx engineering for growth factor patterning in embryoid bodies
Year: 2020
Type: article
Abstract: Growth factor (GF) patterning in stem cell spheroids, such as embryoid bodies (EBs), has been sought to guide their differentiation and organization into functional 3D tissue models and organoids. Current approaches relying on exposure of EBs to gradients of GFs suffer from poor molecular transport in the spheroid microenvironment and from high cost of production and low stability of recombinant GFs. We have developed an alternative method for establishing GF gradients in EBs utilizing stem cell surface engineering with membrane-targeting heparan sulfate-glycomimetic co-receptors for GFs. We have capitalized on the ability of amphiphilic lipid-functionalized glycopolymers with affinity for FGF2 to assemble into nanoscale vesicles with tunable dimensions and extracellular matrix penetrance. Upon size-dependent diffusion into EBs, the vesicles fused with the plasma membranes of stem cells, giving rise to concentric gradients of cells with enhanced FGF2-binding. The extracellular matrix-assisted cell surface remodeling process described is the first example of spatially-targeted glycocalyx engineering in multicellular systems to control GF localization. The glycopolymer structure, vesicle dimensions, and remodeling conditions determine the level of FGF2 adhesion and gradient slope. The increased chemical and thermal stability of the synthetic glycomimetics and the tunability of their GF-binding profile, which is defined by their glycosylation and may be extended to other recombinant or endogenous morphogens beyond FGF2, further increase the versatility of this method.
Source: Biomaterials Science
DOI: 10.1039/d0bm01434f
Institution: University of California San Diego
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Science Foundation, U.S. Department of Education, Alfred P. Sloan Foundation, Research Corporation for Science Advancement, Thailand Science Research and Innovation, National Institutes of Health, University of California, San Diego, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, Division of Electrical, Communications and Cyber Systems, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1429584180, G1589343018, G1699492418, G1884000469, G252083234, Glycan Modulation of Inflammatory Responses, NNCI: San Diego Nanotechnology Infrastructure (SDNI), G5285237269, G5523730667, In vivo glycan engineering at the cell-matrix interface to control stem cell fate, University of California San Diego Neuroscience Microscopy Imaging Core, G639426234
OpenAlex ID: W3111226240