Giant Unilamellar Vesicles (GUVs) are artificial vesicles of spherical shape that can be created from cholesterol and natural nontoxic phospholipids. Due to their size, hydrophobic and hydrophilic fluidic-like membranes character, they are increasingly explored in systems for drug delivery as well as membrane-receptor interaction studies. All cells and associated surface proteins are glycosylated (the glycocalyx) to at least 80% and interaction and adhesion between cells and pathogens occur primarily via protein receptors and carbohydrate ligands. Many non-cell based systems are usually composed of artificial rigid surfaces with little resemblance of cell membrane texture. The importance of in-plane mobility and flexibility of cell surface bound glycoprotein and glyco-lipid ligands is becoming recognized as important features in interaction studies and can optimally be studied when the ligands are integrated into a membrane. In addition, difficulties of low affinity require a high concentration of correctly oligomerized surface ligands in a manner that is difficult to reproduce on a rigid surface. Therefore, it is of major interest to evaluate such interaction in as close proximity to cell-like environment as possible, and this can be mastered by the use of GUVs, which are in the size range of human cells.
In this interdisciplinary project we will design and create a modular toolbox of synthetic glycocalyx components such as lipid-linked glycans, glycopeptides, glycoproteins and antibodies for systematic investigation of GUV cell-surface interactions. Specifically, we will apply this novel toolbox to investigate the principles of (1) cell-cell interactions, (2) cell-pathogen interactions and (3) design specific in-vivo delivery systems for therapeutics.