Continuous Uptake or Saturation - Investigation of Concentration and Surface Packing-Specific Hemin Interaction with Lipid Membranes

Drug design and targeted delivery in cells serve as a flourishing area not only for scientific inquiry, owing to numerous clinical applications, but also for understanding cell interaction with exogenous materials. The membrane localization of heme and its analog hemin, one of the most biologically relevant planar organic molecule, is very important to understand the molecular mechanism of intercalation and adsorption of this cytotoxic molecule after its dissociation from proteins like hemoglobin. Herein, we investigate the differential behavior of hemin on the soft membrane surfaces of phospholipids by synchrotron-based x-ray scattering techniques, Langmuir monolayer measurements and molecular dynamics simulation. A continuous hemin uptake from the subphase and intercalation into and/or adsorption on to the membrane surface have been witnessed in a strongly membrane surface packing-specific manner. Competitive interactions between hemin-membrane and hemin-hemin are proposed to be responsible for the crit...