Pattern formation of lipid domains in bilayer membranes

Abstract

Phase separation plays an important role in spatial organization and material distribution of biological membranes, which are essential for crucial biological functions ranging from signaling and stress response to vesicle trafficking. Domains arising from demixing of molecules coarsen indefinitely unless growth is arrested at a finite size by additional mechanisms (e.g., membrane elasticity). The resulting finite-size domains self-organize into regular patterns such as stripes and dots, which are called modulated phases. Here, we examine the size and morphology of lipid domains with a minimal theoretical model that considers both the elastic deformation of the membrane and the chemical interactions between lipids, which are coupled by a preferred membrane curvature that depends on the local lipid composition. Microscopically, the coupling is caused by an asymmetry between leaflets which emerges after extra lipids (e.g., DPPC) are introduced to the outer leaflet. The additional lipid partitions preferentially to domains where it is enriched, creating a preferred curvature that depends on local composition. We use an amplitude expansion to determine the domain size and morphology of patterns that minimize the total free energy, which is validated by numerical simulations and compared against experiments in synthetic model membranes and cell-derived membranes. The morphology of patterns varies with membrane lipid composition following a complex morphological diagram, which is in good agreement with experiments. The domain size decreases monotonically with a membrane bending modulus but can be non-monotonic with surface tension. Our results offer testable predictions, such as pattern hysteresis upon cycling external stimuli, diverse pattern morphology near critical points, and non-monotonic dependence of the domain size on osmotic pressure, which motivate future experiments. The presented theoretical framework is generally applicable to pattern formation on deformable surfaces.