Glycoscapes: Biomechanical Glycocalyx Models for T-cells

Our immune system relies on a set of powerful defenders called T-cells, which identify and respond to harmful invaders, such as viruses and bacteria. These immune warriors can detect even the smallest differences between dangerous foreign particles and the bodys own cells, an essential skill for preventing disease while avoiding attacks on healthy tissue. T-cells can be imagined as careful inspectors tiptoeing through a dense forest, scanning the environment to spot signs of intruders. On their way through the body, they probe their environment with small finger-like structures called microvilli. If they find a target, they immediately stop their movement and start the immune response, which could either lead to the target cells death or the initiation of other immune functions. Before T-cells microvilli get in contact with the target cells surface, it encounters a physical barrier known as the glycocalyx, which is a thick sugar coating covering all cells. It can act as a protective layer, making it difficult for T-cells` microvilli to reach through and detect pathogens hidden underneath it. Especially tumour cells which are known to use this layer to their advantage by altering it to evade T- cells detection. To better understand this important interaction, we (Dr. Janett Göhring, an immunologist from the BOKU Vienna, and Dr. Dmitry Sivun, a physicist from the University of Applied Sciences Upper Austria) are teaming up to create a unique test model for T-cell probing, which is in essence a simplified yet highly customizable version of the glycocalyx barrier. The proposed technology will use lipid bilayers spanned on microscopic slides, which will be decorated with known components of the glycocalyx covering stimulating agents for T-cells. This technique allows precise changes in thickness, stiffness, and molecular composition of the glycocalyx which enables us to perform systematic tests. T-cells will then be added on top of these models, and their immune functions and shape of the microvilli will be monitored by advanced microscopy. We intend to study how variations in the glycocalyx may affect the ability of T-cells to recognize and respond to threats. By adjusting the mechanical and chemical characteristics of this artificial glycocalyx, we will measure how effectively T-cells can extend their microvilli. The results from this study will create insights into the mechanism of immune surveillance, potentially allowing for the creation of novel therapeutic approaches to help T-cell performance against infections and cancers. Beyond immunology, this versatile platform promises exciting applications across several areas of biomedical research, and to gain new insights into immune cellular interactions at the smallest scales.

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