Thermodynamic and Morphological Properties of Trastuzumab Regulated by the Lipid Composition of Cell Membrane Models at the Air-Water Interface

Abstract

Trastuzumab (Tmab) is an antibody with anti-cancer properties, whose action occurs when the tumor is associated to the overexpression of the human epidermal growth factor receptor. This drug binds to the receptor, blocking downstream signaling pathways, which controls the cancer progression. Tmab also interacts with glycosaminoglycans and proteoglycans of the cell surface and extracellular matrix so that this interaction helps control cellular events in tumorigenic endothelial cells. In this sense, it is interesting, to study the action of this drug in cellular membrane models to understand its action in cellular membranes and in other lipid surfaces with pharmaceutical interest. In this work, Tmab was incorporated in lipid monolayers at the air-water interface and their thermodynamic, morphological and structural effects were investigated with tensiometry, Brewster angle microscopy (BAM) and polarization-modulation reflection-absorption infrared spectroscopy (PM-IRRAS), respectively. For that, we employed the phospholipids dipalmitoylphosphatidylcholine (DPPC), and dipalmitoylphosphoethanolamine (DPPE), and their mixtures with cholesterol. Tmab expanded all lipid films and affected the compressional and structural properties as observed by surface pressure isotherms, in-plane elasticity, and PM-IRRAS, respectively. BAM showed distinctive morphological patterns for the monolayers and infrared spectroscopy showed an increased number of gauche conformers related to the CH2 stretching mode, indicating film molecular disorder. Also, the antibody kept the beta-sheet structure of the polypeptide backbone adsorbed at the lipid monolayers though the secondary conformation changed according to the monolayer composition. The results then suggest that the membrane lipid profile affects the adsorption of Tmab at lipid monolayers, which can be associated to the fact that antibody-receptor interactions at the lipid membrane environment can possibly be tuned by changing the lipid composition at the receptor vicinity.