c-Fos and phosphatidylinositol-4,5-bisphosphate reciprocally reorganize in mixed monolayers

The transcription factor c-Fos has surface thermodynamic properties that allow it to differentially interact with phospholipids, especially PIP2. It regulates phospholipid metabolism both in vivo and in vitro, and modulates degradation of phospholipid monolayers by phospholipases in a way that depends on the membrane intermolecular packing (i.e., surface lateral pressure). With the aim to understand details of the interactions of c-Fos at the membrane level, we studied the surface packing, dipole potential, compressibility and topography of mixed films of the protein with PIP2. We show that c-Fos changes the packing of liquid-expanded PIP2 monolayers, in a different manner with respect to its effect on the similarly liquid-expanded dilauroylphosphatidylcholine monolayers. The changes at the local molecular level are transduced to long-range inhomogeneities of the surface, detected by Brewster angle (BAM) and epifluorescence microscopy (EFM). Our results highlight the capacity of c-Fos to alter the packing and dipole potential of the lipid-protein interface. This involves variations of the surface in-plane elasticity and lateral segregation of phase domains. These dynamic, reversible alterations of surface organization provide a basis by which c-Fos may transduce molecular information at the membrane level.