Key Factors Regulating the Mass Delivery of Macromolecules to Model Cell Membranes: Gravity and Electrostatics

We show that both gravity and electrostatics are key factors regulating interactions between model cell membranes and self-assembled liquid crystalline aggregates of dendrimers and phospholipids. The system is a proxy for the trafficking of reservoirs of therapeutic drugs to cell membranes for slow diffusion and continuous delivery. Neutron reflectometry measurements were carried out on supported lipid bilayers of varying charge and on hydrophilic silica surfaces. Translocation of the macromolecule across the membrane and adsorption of the lamellar aggregates occur only when the membrane (1) is located above the bulk liquid and (2) has sufficient negative charge. The impact of such dramatic directionality effects due to bulk phase separation and gravity is emphasized for future biochemical investigations. Further, the potential to switch on the interaction mechanism through tuning the charge of the aggregates to activate endocytosis pathways on specific cell types is discussed in the context of targeted drug delivery applications.