Glycoscapes: Biomechanical Glycocalyx Models for Surveilling T-Cells

T-cells patrol body tissues in search of pathogen-derived antigens, recognizing and destroying infected cells and aiding B-cells in antibody production. A frequently overlooked factor in this process is the glycocalyx—a dense carbohydrate coat surrounding all cells, forming a mechanical barrier for the antigen-scanning microvilli of T-cells. These protrusions penetrate the barrier, enabling interaction between the T-cell receptor and the target cell’s MHC. The glycocalyx’s biochemical complexity and architecture influence its mechanical properties. This project employs a novel lipid bilayer platform to mimic the glycocalyx as a chemically active, mechanical barrier and to study its effect on antigen recognition. Our model features three orthogonal functional groups on lipids, enabling control over lipid composition and incorporation of relevant ligands such as proteins, glycosaminoglycans, or proteoglycans. The research will address two key aims: (i) creating a robust lipid bilayer-anchored glycocalyx replicating the height, composition, and elasticity of natural glycocalyces, and (ii) investigating how glycocalyx density and stiffness affect T-cell microvilli dimensions and dynamics, and thus immune surveillance. Our approach allows consistent integration of major glycocalyx components, including hyaluronans, glycosaminoglycan-bearing proteoglycans, as well as T-cell receptor ligands and adhesion factors. We will provide nanoscale quantification of their impact on antigen sensitivity and microvilli structure. This work will shed light on early T-cell activation in relation to glycocalyx composition, architecture, and elasticity. The versatile platform, with tunable chemical and mechanical properties, also holds promise for use in other biological models. The project is led by Dr. Janett Goehring (BOKU Vienna) and Dr. Dmitry Sivun (University of Applied Sciences Upper Austria), with support from Prof. (FH) PD. Dr. Jaroslaw Jacak (University of Applied Sciences Upper Austria).