The lipid composition affects Trastuzumab adsorption at monolayers at the air-water interface.

Trastuzumab (Tmab), an antibody for breast cancer, was incorporated in Langmuir monolayers with different lipidic compositions to investigate the drug action in lipidic interfaces of pharmaceutical interest. Tmab caused all lipid films to expand as confirmed with by surface pressure-area isotherm, proving its incorporation. It also affected the compressional and structural properties as observed by in-plane elasticity curves and polarization modulation reflection-absorption infrared spectroscopy (PM-IRRAS), respectively. Although Tmab did not change significantly the compressional modulus for dipalmitoylphosphatidylcholine (DPPC) monolayers, it decreased it for the mixtures of DPPC with cholesterol. In contrast, for dipalmitoylphosphoethanolamine (DPPE), Tmab increased the compressional modulus for both monolayers, pure DPPE or mixed with cholesterol. While Brewster Angle Microscopy showed discrete distinctive morphological patterns for the monolayers investigated, PM-IRRAS showed that Tmab caused an increased number of gauche conformers related to the CH2 stretching mode for the lipid acyl chains, suggesting molecular disorder. Furthermore, the antibody kept the ß-sheet structure of the polypeptide backbone adsorbed at the lipid monolayers although the secondary conformation altered according to the film composition at the air-water interface. As a result, the results suggest that the membrane lipid profile affects the adsorption of Tmab at lipid monolayers, which can be important for the incorporation of this drug in lipidic supramolecular systems like in liposomes for drug delivery and in biomembranes.

Interaction of Trastuzumab with biomembrane models at air-water interfaces mimicking cancer cell surfaces.

Trastuzumab (Tmab) is a monoclonal antibody administered as targeted therapy for HER2-positive breast cancer whose molecular interactions at the HER2 receptor microenvironment are not completely clarified yet. This paper describes the influence of Tmab in the molecular organization of films of biological-relevant molecules at the air water interface. For that, we spread components of tumorigenic and non-tumorigenic cells directly on the air-water interface. The physicochemical properties of the films were investigated with surface pressure-area isotherms and Brewster angle microscopy, and distinction between the cellular lines with higher or lower amount of HER2 could be detected based on the physicochemical properties of the interfacial films. The systems organized at the air-water interface were transferred to solid supports as Langmuir-Blodgett films and the nano-scale morphology investigated with atomic force microscopy. The overall results related to Tmab interacting with the films lead to the conclusion that Tmab tends to condense rich-HER2 films, causing irregular dimerization of the receptor protein, changing the membrane topography of the films, with formation of phases with different levels of reflectivity and aggregation morphology, and finally revealing that the interaction of the antibody with proteo-lipidic biointerfaces is modulated by the film composition. We believe that novel perspectives concerning the molecular interactions in the plasma membrane microenvironment through Langmuir monolayers can be obtained from this work in order to enhance the Tmab-based cancer therapy.