Self-organized pattern formation of a lipid kinase/phosphatase system in vitro

Lipid kinases and phosphatases involved in signal transduction, cytoskeletal organization, and membrane trafficking often show spatiotemporal dynamics. The mechanisms governing these dynamics and their downstream effects remain enigmatic. Recently, a phosphatidylinositol (PI) lipid kinase, MavQ, and a phosphatase, SidP, two effector proteins of the intracellular pathogenic bacterium Legionella pneumophila, have been shown to remodel ER membranes of the eukaryotic host cell, while exhibiting oscillatory dynamics. Here we reconstitute this minimal system in vitro. Purified MavQ and SidP self-organize into traveling surface waves and other patterns on supported lipid bilayers containing PI lipids. By varying protein and lipid concentrations, we acquire phase diagrams that reveal distinct behaviors and show that the protein patterns enrich and transport the substrate lipid. By patterning the underlying membrane, we characterize the sensitivity of the system to the confining geometry. Finally, to capture our experimental observations and define the underlying mechanism, we develop a continuum theoretical model. In summary, we introduce a new paradigm for the study of protein self-organization on membranes, which produces patterns and behaviors that are distinct from established systems such as E. coli MinDE.