Cell membranes form a highly complex and heterogeneous mixture of membrane proteins and lipids. Understanding the protein-lipid interplay that gives rise to the lateral organisation principles of cell membranes is essential for life and health, as malfunctioning at the level of lipid-protein interaction is implicated in numerous diseases1, including various cancers, Alzheimer’s disease, diabetes, HIV, and heart failure. Thus, investigations of these crowded membranes is emerging as a new and exceptionally exciting frontier at the crossroads of biology, life sciences, physics, and chemistry.
However, our current understanding of the detailed organisation of cellular membranes, remains rather elusive. Characterisation of the structural heterogeneity in-vivo is very challenging, owing to the lack of experimental methods suitable for studying these fluctuating nanoscale assemblies of lipids and proteins in living cells with the required spatio-temporal resolution. Given the fundamental role of biomembranes, both within and around the cell, knowledge about the molecular level organisation is crucial. In recent years, computer simulations have become a unique investigatory tool for understanding the driving forces governing the lateral organisation of cellular membrane components and this “computational microscopy” has become indispensable as a complement to traditional microscopy methods.
In this ERC project, using advanced computational microscopy, we studied the interaction of lipids and proteins in complex, crowded, membrane patches, to enable the driving forces of membrane protein sorting and clustering to be unravelled at conditions closely mimicking real cellular membranes.
