Cell surface glycoproteins and glycans play critical roles in a range of physiological functions and disease processes, are valuable drug targets, and may be exploited as biomarkers for precision medicine. Despite their biological relevance and utility, glycoproteins and glycans are often understudied largely due to technical challenges. This presentation will describe CellSurfer and glyPAQ, new analytical platforms that enable rapid identification and quantification of cell surface glycoproteins and glycans from small sample sizes. The application of these new methodologies to address outstanding questions in cardiac physiology and disease, with an emphasis on precision medicine, will be described. CellSurfer enables routine mass spectrometry-based discovery of cell surface N-glycoproteins from samples with limited availability (100-1000 μg or 300,000 – 10 million cells) with &gt;80% specificity. Innovative bioinformatic tools expedite discovery, analysis, annotation, and candidate prioritization for downstream validation. The CellSurfer platform, from sample preparation to candidate prioritization, can be completed in 3 workdays and enables the discovery and quantification of cell surface N-glycoproteins to support the development of immunophenotyping strategies, identification of drug delivery targets, and for studying biological and disease processes. We applied CellSurfer to cells isolated from cardiac tissue to develop the first cell type-specific maps of the cell surface N-glycoproteome of adult human cardiomyocytes from five myocardial chambers. Primary explanted cardiac fibroblasts, cardiac microvascular endothelial and coronary artery smooth muscle cells were also profiled. Novel insights into cardiac fibroblast surfaceome dynamics due to extended culturing were revealed. New cardiac cell-type specific markers also emerged. glyPAQ enables standardized processing of biological samples for quantitative profiling of native N- and O-glycan structures by mass spectrometry. glyPAQ is suitable for the preparation of a broad range of sample complexities, including monoclonal antibodies, cells, tissues, serum, plasma, and urine. We applied glyPAQ to human serum and tissue to inform new precision medicine strategies for patients at increased risk for cardiovascular disease due to rheumatoid arthritis and generate new insights into the impact of COVID-19 infection on the human heart.

CellSurfer & glyPAQ: New technologies for exploiting the human glycoproteome for personalized medicine

ACS Spring 2022

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