Biological Membranes in Action: A Unified Approach to Complexation, Scaffolding and Active Transport
In recent breakthrough publications, the effect of fluctuations on the affinity of membrane-confined molecules has been evaluated, and a quantitative model for the time evolution of small adhesion domains has been developed under my leadership. Now I propose to bring my research to a new level by tackling the problem of active and passive organisation of proteins into macromolecular structures on fluctuating fluid membranes, using a physicist’s approach across established disciplinary boundaries.The formation and transport of supramolecular complexes in membranes is ubiquitous to nearly all functions of biological cells. Today, there is a variety of experiments suggesting that macromolecular complexes act as scaffolds for free proteins, overall yielding obstructed diffusion, counterbalanced by active transport by molecular motors. However, an integrative view connecting complexation and transport is largely missing. Furthermore, the effects of membrane mediated interactions and (non)-thermal fluctuations were so far overlooked. Gaining a quantitative insight into these processes is key to understanding the fundamental functioning of cells.Together with my carefully selected team, I will address these intrinsically biological problems, by means of theoretical physics. Phenomena such as active and anomalous transport, as well as complexation are also currently subject to intense research in the statistical and soft matter physics communities. In this context, the aim of this proposal is to bridge the divide between the two worlds and significantly contribute to both physics and the life sciences by developing general principles that can be applied to processes in cells. Resolving these issues is of fundamental importance since it would identify how interactions on the cell surface arise, and may translate directly into pharmaceutical applications.