Novo Nordisk Fonden - A multidisciplinary platform for revealing mechanisms of annexin-mediated plasma membrane repair

The plasma membrane of eukaryotic cells constitutes the essential physical barrier that separates the interior structures of a cell from the extracellular environment. Unlike prokaryotic cells, which are protected by a cell wall, mammalian cells are more exposed and vulnerable to cell death induced by membrane injuries. Thus, eukaryotic cells have developed efficient repair mechanisms to cope with membrane disruptions. However, in spite of its essential function for cell life the physical and molecular mechanisms behind plasma membrane repair are, as yet, not well characterized. Our recent studies show that enhanced plasma membrane repair involving biophysical manipulation of membranes is important for the survival of cancer cells to counteract membrane lesions induced by enhanced metabolic stress, membrane dynamics, and during invasion through dense extracellular matrix. This research proposal aims at elucidating fundamental biophysical mechanisms of plasma membrane repair with particular focus on how cancer cells cope with membrane disruptions involving annexin proteins. Moreover, we will examine the role of membrane repair mechanisms to cope with the effects of pore-like assemblies formed by small peptide oligomers in the plasma membrane, which are considered the primary neurotoxic species at work in Alzheimer’s disease and other neurodegenerative disorders. The project critically depends on the interdisciplinary expertise available at the respective institutions: Danish Cancer Society Research Center (DCRC), Niels Bohr Institute (NBI) and University of Southern Denmark (SDU) forming a synergy network between molecular biology (DCRC), experimental physics involving optical manipulation of membranes (NBI), surface science (SDU), and computer simulations (SDU). The interdisciplinary nature of this project will provide a unique platform for
discovering mechanisms of plasma membrane repair and to reveal novel avenues to treat cancer and neurodegenerative diseases.