1. Clustering of Major Histocompatibility Complex-Class I Molecules in Healthy and Cancer Colon Cells Revealed from Their Nanomechanical Properties
- Author
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Manola Moretti, Claudio Canale, Bruno Torre, Mario Malerba, Enzo Di Fabrizio, Rosanna La Rocca, Michela Perrone Donnorso, Gobind Das, Ennio Carbone, Adnane Achour, Cinzia Garofalo, Rosa Sottile, and Klas Kärre
- Subjects
AFM ,MHC-I clustering ,cancer cells ,nanomechanical properties ,single molecule force spectroscopy ,Colon ,T cell ,Cell ,Antigen-Presenting Cells ,General Physics and Astronomy ,chemical and pharmacologic phenomena ,02 engineering and technology ,010402 general chemistry ,Major histocompatibility complex ,01 natural sciences ,Major Histocompatibility Complex ,Cluster Analysis ,Histocompatibility Antigens Class II ,Histocompatibility Antigens Class I ,Neoplasms ,Immune system ,medicine ,General Materials Science ,biology ,Chemistry ,T-cell receptor ,General Engineering ,Force spectroscopy ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Cell biology ,medicine.anatomical_structure ,Cell culture ,Cancer cell ,biology.protein ,0210 nano-technology - Abstract
The activation of the T cell mediated immune response relies on the fine interaction between the T cell receptor on the immune cell and the antigen-presenting major histocompatibility complex (MHC) molecules on the membrane surface of antigen-presenting cells. Both the distribution and quantity of MHC/peptide complexes and their adequate morphological presentation affect the activation of the immune cells. In several types of cancer the immune response is down-regulated due to the low expression of MHC-class I (MHC-I) molecules on the cell's surface, and in addition, the mechanical properties of the membrane seem to play a role. Herein, we investigate the distribution of MHC-I molecules and the related nanoscale mechanical environment on the cell surface of two cell lines derived from colon adenocarcinoma and a healthy epithelial colon reference cell line. Atomic force microscopy (AFM) force spectroscopy analysis using an antibody-tagged pyramidal probe specific for MHC-I molecules and a formula that relates the elasticity of the cell to the energy of adhesion revealed the different population distributions of MHC-I molecules in healthy cells compared to cancer cells. We found that MHC-I molecules are significantly less expressed in cancer cells. Moreover, the local elastic modulus is significantly reduced in cancer cells. We speculate that these results might be related to the proven ability of cancer cells to evade the immune system, not only by reducing MHC-I cell surface expression but also by modifying the local mechanical properties affecting the overall morphology of MHC-I synapse presentation to immune cells.
- Published
- 2021
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