Phosphatidylserine lipids reduce the adsorption of chondroitin sulphate at the membrane surface

Hypothesis Chondroitin sulphate (CS) is a linear polysaccharide typically found on the surface of cells and contributing to the structure of the extracellular matrix. Because of its proximity to the plasma membrane, the outermost cellular barrier, CS can interact with the phospholipids forming the structural scaffold of this cellular membrane. We hypothesise that the lipid composition of the plasma membrane, and specifically the exposure of phosphatidylserine (PS) lipids (an event that is detected in cancer cells and also associated to apoptosis and inflammation), affects the structural conformation of CS at the cell surface. Experiments We combined experimental data obtained with different techniques, i.e., quartz crystal microbalance with dissipation monitoring, neutron reflectometry and infrared spectroscopy, with molecular dynamics (MD) simulations to investigate the adsorption of CS at the surface of lipid bilayers prepared with either phosphatidylcholine (PC) lipids or a mixture of PC and PS lipids. Experiments were designed to identify the molecular groups that are involved in the CS-lipid interaction. Findings Our results indicate that CS adsorbs and remains stably attached to the lipid bilayer without PS lipids, due to stabilising interactions between the negatively charged sulphate groups on CS and positively charged choline groups within PC. The addition of POPS strongly reduces the CS-bilayer association: detecting experimentally CS chains attached to the bilayer was challenging, and the MD simulations suggest a weaker binding of CS to a PC-PS membrane.