One of the key characteristics of life is the existence of a boundary that delineates the organism from its outer environment. The boundary membrane structure that defines all cells is called the plasma membrane. In eukaryotic cells, membranes also divide the internal space into discrete compartments, organelles, to segregate processes and components. The lipid membrane bilayer serves also as a matrix for a multitude of membrane proteins. The membrane proteins are known to be key molecules for plenty vital cellular functions: transport, energy transduction, signaling, and communication, to name a few. The functional importance of membrane proteins explains why a lot of pathologies are related to disorders at the membrane protein level. Notably ~60% of nowadays drugs target membrane proteins, underlining the medical importance of this class of proteins. Therefore, studies of disorders at the level of membrane proteins and their organisation within the membrane are essential to provide novel strategies for the effective treatment of illness.

At present about 300 unique membrane protein structures have been solved. The difficulty for membrane protein crystallisation is hidden in the amphiphilic nature of these molecules, however technical problems are being overcome by modern crystallisation methods, as visible from the exponential increase of solved structures. Therefore, in future studies the focus shall be shifted onto interaction dynamics, conformational changes and supramolecular complexes of membrane proteins. The final goal being to acquire a dynamic and integrated view of the native bio-membrane. These objectives demand the performance of imaging the membrane at high spatio-temporal resolution, at a high signal-to-noise ratio, in a native-like environment. Unfortunately, to date, this seems impossible…

The atomic force microscope (AFM) fulfils many of the above-mentioned criteria. In particular, the recent development of high-speed atomic force microscopy (HS-AFM) allows now individual molecules to be imaged dynamically in physiological environment. AFM can also be operated in force spectroscopy mode and analyse the physics of the interactions between and within proteins in great detail.


Hence, it is our aim to overcome AFM-related technical and biological bottlenecks to provide first high-resolution dynamic views of complex protein samples, and of membranes extracted from cells and on cells in particular. On the way to there, we aim at gathering a deeper understanding of the structure, conformational changes, the dynamics and interactions within and between protein complexes to get insights into the driving forces that are responsible of higher order organization and the processes in live cells.