Hydrodynamics of Double Membrane Spreading in Biology

ended

Eukaryotic cells exist in highly dynamic environments and are subject to a variety of existential threats, ranging from viruses to pathological defects in their own genome. To cope with these challenges, cells have developed a conserved pathway in order to degrade harmful objects internal to the cell. This process is know as autophagy. Autophagy involves the formation of a double lipid membrane compartment that wraps around harmful targets, such as damaged organelles, protein aggregates or lipid droplets in order to facilitate their degradation. Although the genetic and molecular triggers for autophagy have been analysed in much detail, the biophysical principles governing such a dynamic process have received remarkably little attention. The biophysics of autophagy is highly complex biophysical process, involving the driven, non-equilibrium morphodynamics of a fluid membrane that must wrap its target. This incorporates molecular signalling and adhesion, vesicular trafficking and active force generation and complex flows of the lipid membrane in curved geometries as well as the Stokesian hydrodynamics of the embedding fluid. This makes the dynamics of autophagy essentially a problem of active soft matter physics. In HYDROBIOMEM I will build on demonstrable expertise in active soft matter physics, morphology and fluid dynamics to develop novel theoretical and computational models to give mechanistic understanding and predictions of the dynamics of double membrane wrapping in autophagy. I will apply these tools, in close collaboration with experimentalists, to test existing biological hypotheses and give new insight into this ubiquitous process in cell biology.