Alexander Cartagena-Rivera, Ph.D, Chief of NIBIB’s Section on Mechanobiology

Speaker:

Alexander Cartagena-Rivera, Ph.D.

Chief of NIBIB’s Section on Mechanobiology

National Institute of Biomedical Imaging and Bioengineering

Faculty Host: Beth Pruitt

Title: Aberrant glycosylation regulates membrane surface architecture and viscoelasticity of pancreatic cancer cells

Abstract: 

The cellular glycocalyx plays a crucial role in making pancreatic cancer one of the deadliest
malignancies globally. It complicates early detection and reduces the effectiveness of
conventional therapies. In pancreatic cancer, the components of the glycocalyx are often
upregulated or abnormally glycosylated, promoting tumor progression through immune
evasion, enhanced metastasis, and drug resistance. While these biochemical effects are
known, the biophysical impact of the glycocalyx on cancer cells is less understood. In our
study, we explored the structural and biomechanical effects of modifying the glycocalyx
architecture in pancreatic cancer cells using various chemical compounds. We employed a
recently developed Atomic Force Microscopy nanomechanical mapping method to visualize
cellular mechanical heterogeneities in a high spatiotemporal context. Our new approach
allows for the viscoelastic inversion of high-resolution spatiotemporal data at rates which are
orders of magnitude faster (more than 37,386-fold) than optimizing a traditional rheological
model for each pixel. Then, we investigated the architectural and biophysical effects of
glycocalyx architectural modulation in pancreatic cancer cells. Perturbations of hyaluronic
acid (HA), sialic acid (SA), mucins, and N-glycans through enzymatic treatments led to
significant architectural remodeling of the cell surface. Interestingly, removal of SA and
mucins resulted in a softer and more fluid cell surface, while removal of HA softened and
increased viscosity. In addition, preliminary cytokine expression results suggested that SA
removal leads to a pronounced pro-inflammatory response (IL-2, IL-8, INF-γ among others)
of human cytotoxic CD8+ T Lymphocytes, greater than removing other glycocalyx
components. Lastly, a glycomics study also revealed unique changes in the structure of N- and
O-glycans, with significantly more heterogeneity in the structure of N-glycans on pancreatic
cancer cells, and O-glycans showing a particularly higher degree of SA deposition. Our
findings suggest that the glycocalyx of human pancreatic ductal adenocarcinoma cells
fundamentally regulate extracellular surface architecture, mechanical properties, composition,
and function, thereby promoting tumor progression and metastasis by acting as a physical
barrier to antitumor responses.

Bio:

Dr. Alexander X. Cartagena-Rivera received a Ph.D. in Mechanical Engineering from Purdue University in 2014. Dr. Cartagena-Rivera joined the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health as an Earl Stadtman Tenure-Track Investigator position in 2019. He is now chief of NIBIB’s Section on Mechanobiology, where he and his lab staff continue work on understanding cellular and tissue molecular-mechanical regulation and development of advanced atomic force microscopy technologies for cancer biology and hearing research.