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

    Year: 2019

    Journal: Biochim. Biophys. Acta-Biomembr., Volume 1861, 1-Oct

    Authors: Sakai, Andrei; de Sousa Mesquita, Ana Paula; de Castro Levatti, Erica Valadares; Straus, Anita Hilda; Nader, Helena B.; Lopes, Carla Cristina; Caseli, Luciano

    Organizations: Fundacao de Amparao Pesquisa do Estado de Sao Paulo, FAPESPFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2015/23446-0, 2013/14262-7, 2019/03239-0]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPqNational Council for Scientific and Technological Development (CNPq) [400896/2016-8]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, CAPESCAPES [001]

    Keywords: Trastuzumab; Langmuir monolayers; Microdomain; Phase separation; Membrane receptors; Membrane models

    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 nanoscale 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.
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