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

Autor(es)

Sakai, Andrei ^[1] ; de Sousa Mesquita, Ana Paula ^[2] ; de Castro Levatti, Erica Valadares ^[2] ; Straus, Anita Hilda ^[2] ; Nader, Helena B. ^[2] ; Lopes, Carla Cristina ^{[2, 1]} ; Caseli, Luciano ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Rua Sao Nicolau 210, BR-09972270 Diadema - Brazil

^[2] Univ Fed, Dept Bioquim, Escola Paulista Med, Rua Pedro de Toledo 669, BR-04039032 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES; v. 1861, n. 10 OCT 1 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 19/03239-0 - Interfaces nanoestruturadas para a investigação de substâncias bioativas em modelos de membrana celular e para a construção de dispositivos optoeletrônicos enzimáticos
• Beneficiário: Luciano Caseli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/23446-0 - Superfícies inteligentes nanoestruturadas e bioinspiradas: investigação de interações em modelos de membrana e produção de dispositivos para biossensores e análise ambiental.
• Beneficiário: Luciano Caseli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/14262-7 - Filmes nanoestruturados de materiais de interesse biológico
• Beneficiário: Osvaldo Novais de Oliveira Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático