Biology subjects

Moeckl, L.

Publications and source records attributed to Moeckl, L..

3 recordsLinked to original sources

bioRxiv2025

Glycan Atlassing: Nanoscale analysis of glycocalyx architecture enables functional tracing of cell state

The glycocalyx is a complex layer of glycosylated biomolecules surrounding all cells in the human body. It is involved in the regulation of critical cellular processes such as immune response modulation, cell adhesion, and host-pathogen interactions. Despite these insights, the functional relationship between glycocalyx architecture and cellular state has remained elusive so far, mainly attributable to the structural diversity of glycocalyx constituents and their nanoscale organization. Here, we show that DNA-tagged lectin labeling and metabolic oligosaccharide engineering enables multiplexed super-resolution microscopy of glycocalyx constituents, yielding an atlas of glycocalyx architecture with nanometer resolution. Quantitative analysis of the obtained nanoscale map of glycocalyx constituents facilitates the extraction of characteristic spatial relationships that accurately report on cellular state. We demonstrate the capacity of our approach, which we term Glycan Atlassing, across cell and tissue types, ranging from cultured cell lines to primary immune cells, neurons, and primary patient tissue. Glycan Atlassing establishes a powerful strategy for investigating glycocalyx remodeling in development and disease, potentially enabling the development of new glycocalyx-centered targets in diagnosis and therapy.

biophysics↗

bioRxiv2025

Angstrom-resolution imaging of cell-surface glycans

Glycobiology is rooted in the study of monosaccharides, [A]ngstrom-sized molecules that are the building blocks of intricate glycosylation patterns. Glycosylated biomolecules form the glycocalyx, a dense coat encasing every human cell with central relevance - among others - in immunology, oncology, and virology. In order to understand glycosylation function, visualizing its molecular structure is fundamental. However, the ability to visualize the molecular architecture of the glycocalyx has remained elusive. Techniques like mass spectrometry, electron microscopy, and fluorescence microscopy lack the necessary cellular context, specificity, and resolution. Here, we address these limitations by combining metabolic labeling with [A]ngstrom-resolution fluorescence microscopy, enabling the first-ever visualization of individual sugars within glycans on the cell surface. Our work provides unprecedented insights into the molecular architecture of the glycocalyx and constitutes the foundation for future explorations of its function in health and disease.

biophysics↗

bioRxiv2021

Multi-color super-resolution imaging to study human coronavirus RNA during cellular infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus within 20 years that gave rise to a life-threatening disease and the first to reach pandemic spread. To make therapeutic headway against current and future coronaviruses, the biology of coronavirus RNA during infection must be precisely understood. Here, we present a robust and generalizable framework combining high-throughput confocal and super-resolution microscopy imaging to study coronavirus infection at the nanoscale. Employing the model human coronavirus HCoV-229E, we specifically labeled coronavirus genomic RNA (gRNA) and double-stranded RNA (dsRNA) via multicolor RNA-immunoFISH and visualized their localization patterns within the cell. The exquisite resolution of our approach uncovers a striking spatial organization of gRNA and dsRNA into three distinct structures and enables quantitative characterization of the status of the infection after antiviral drug treatment. Our approach provides a comprehensive framework that supports investigations of coronavirus fundamental biology and therapeutic effects.

cell biology↗