Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

The cell wall, or cell membrane, is composed of a double-layered lipid film and proteins, functional macromolecules that control electrical signals and substrate transport in and out of the cell. Membrane proteins also sense external stimuli and trigger signaling cascades in the inside. Until recently, the lipid membrane itself was considered mainly a passive matrix that separates the cell interior from the exterior. However, recently, it became increasingly clear that the composition of the lipid membrane influences the functioning of the proteins. This also relates to our nutrition; compounds such as cholesterol and omega-3 are known to enter the lipid film, alter its properties and modulate protein function. Conversely, also the proteins embedded in the lipid membrane alter its phase behaviour and form.
Many proteins oligomerize to larger complexes or clusters. We found recently that clustering of a membrane protein, the proton-gated KcsA channels, is related to deformations of the membrane. In this research program, we investigate the energetics of protein oligomerization and membrane deformations and their implication on protein function. We will directly observe the dynamics of protein oligomerization using single molecule fluorescence, where we can follow the movement of the proteins in an artificial membrane and determine the energy landscape of the clustering process. We will determine the effect of membrane curvature on protein function and oligomerization and characterize which classes of membrane proteins undergo lipid-mediated clustering.