Molecular mechanisms of erythrocyte storage lesion: the role of lipid domains

• Applicants: Professorin Dr. Karen Bieback; Kathryn Melzak, Ph.D.
• Subject Area: Hematology, Oncology ; Biophysics
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 290289105

Red blood cells (RBCs) that are stored for transfusions undergo degradation of their lipid bilayers, leading to changes in cell shape. The smooth biconcave disc shape that is found in vivo is lost, and the cells develop into bumpy forms known as echinocytes. The bumps that develop become more prominent as the storage time progresses and are associated with the shedding of potentially harmful microvesicles. The RBCs collected from different donors degenerate at different rates, with a substantial degree of variation that is not attributable to inherited factors. This project has two goals: the first is to identify membrane properties that can be used as markers for RBC ageing, and the second is to investigate the potential links between such properties and the RBC storage quality. The membrane properties that we will investigate are associated with the lateral segregation of lipids into domains having different compositions. Experimental approaches will include the use of fluorescent labels to identify lipid domains. A second experimental approach will be to use atomic force microscopy (AFM) to measure the force required to puncture the cells at defined locations. Investigations will be carried out using a fluorescence microscope that is combined with an atomic force microscope (AFM) so that the fluorescence results could be compared with the AFM breakthrough measurements. Results with RBCs from different donors would be compared with standard assays of RBC storage quality to investigate the extent to which storage quality can be linked to physical parameters describing the membrane properties.

• DFG Programme: Research Grants