Engineering cell membrane by liposomal treatment modulates endocytosis of nanomaterials in tumor cells Abstract: Nanomedicines including liposomes and polymeric nanoparticles can target tumor cells via receptor mediated endocytosis. However the role of biophysics of cell lipid bilayer in nanoparticle uptake pathway remains unexplored. Nanomedicines are taken up mainly via clathrin caveolae mediated endocytosis which depends on membrane deformation. Since phase behavior influences deformability of lipid bilayers we postulated that phase behavior of cell membranes could impact endocytosis of nanomedicines.<br>In second section of the dissertation we inquired whether endocytosis of liposomes a lipid bilayer derived vesicle depends on their phase behavior. First it was shown that the endocytosis of liposomes was related to their phase behavior and increasing membrane fluidity diminished dynamin dependent endocytosis of liposomes. Since liposomal treatment can modify the phase behavior of cell membranes we further theorized that altering phase behavior of cell membranes by liposomal pre treatment could impact endocytosis of nanoparticles. Using rhodamine labeled PLGA nanoparticles and NBD cholesterol labeled liposomes (100 nm) as models for nanomedicine and employing giant plasma membrane vesicles (GPMV) derived from MDA MB 231 as model for the cell membrane the effect of liposomal treatment on nanomedicine uptake as investigated. Characterization of the stiffness of GPMV using flicker spectroscopy revealed that liposomal treatment can modify the stiffness and lipid composition of cell membrane thereby modulating endocytic uptake of PLGA NPs. The increased cell membrane stiffness was found to elevate cellular uptake of NPs by promoting clathrin caveolae dynamin mediated endocytosis.<br>Cellular uptake of lipid vesicles is important for cell communication and drug delivery. Since lipid vesicles can be taken up by the cells upon interacting with plasma membranes in section three of the dissertation it was postulated that the pattern of membrane interaction would determine endocytic uptake mechanism of liposomes. Since cholesterol can influence the phase behavior and curvature of lipid bilayers and thereby impacting interaction between lipid bilayers the role of liposomal free cholesterol in liposome cell interaction was investigated. We found that efficiency of nonspecific membrane interaction was associated with cellular uptake mechanisms of liposomes and liposomal free cholesterol enhanced the non specific liposome cell membrane interaction; resu ...