Clustering of Major Histocompatibility Complex-Class I Molecules in Healthy and Cancer Colon Cells Revealed from Their Nanomechanical Properties

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 downregulated 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.

Supramolecular Combination Chemotherapy: Cucurbit[8]uril Complex Enhanced Platinum Drug Infiltration and Modified Nanomechanical Property of Colorectal Cancer Cells

“…The stiffness of the cellular surface influenced cell adhesion, as stiffer cells were hard to deform and retained more contact area as well as invasion. − We also measured the adhesion force for adherent colorectal cancer cells treated with either CLE or LE drugs. During a 4 h measurement, the adhesion force was 0.161 nN for LE-drug-treated cells compared with a 0.108 nN for CLE-treated cells.…”

Enhancing Cancer Immunotherapeutic Efficacy with Sonotheranostic Strategies

“…The cyclic cascade tumor derived antigens are produced by antigenic presenting cells (APCs) and degrade the endogenous antigens into peptides . The degraded peptides are delivered to the major histocompatible complex I (MHC I) and key histocompatible complex II (MHC II) which present a peptide MHC complex to the effector T cells . T cells are activated by certain costimulatory and coinhibitory molecules along with direct trafficking of T cells to tumor cells for destruction of tumor cells .…”

“…32 The degraded peptides are delivered to the major histocompatible complex I (MHC I) and key histocompatible complex II (MHC II) which present a peptide MHC complex to the effector T cells. 33 T cells are activated by certain costimulatory and coinhibitory molecules along with direct trafficking of T cells to tumor cells for destruction of tumor cells. 34 The dissociation of the tumor increases the exposure for antigen recognition and begins the cascade for a strengthened adaptive immunity.…”

Force Mapping Reveals the Spatial Distribution of Individual Proteins in a Neuron

“…33−37 Recent studies reported the interaction between a membrane receptor and a corresponding ligand through single-cell experiments, 38,39 the binding frequency of target proteins to the receptors on cell surfaces, 40,41 and the interaction density of an antigenpresenting molecule and the related nanomechanical properties of the membrane. 42 However, examining the distribution of individual proteins in local areas of a neuronal cell, such as dendritic spines, has been challenging presumably due to binding events that are either nonspecific or involving multiple molecules interacting together. In this study, we used dendronmodified AFM probes to provide spacing between tethered molecules and increase single-molecule binding probabilities.…”

“…Here, we present a force mapping-based atomic force microscopy (AFM) − approach that directly locates individual proteins at local areas in single cell without any signal amplification or fluorescent labeling. AFM has been a powerful technique to study biological interactions such as antigen–antibody, , ligand–receptor, − and DNA–DNA binding at the single-molecule level. − Recent studies reported the interaction between a membrane receptor and a corresponding ligand through single-cell experiments, , the binding frequency of target proteins to the receptors on cell surfaces, , and the interaction density of an antigen-presenting molecule and the related nanomechanical properties of the membrane . However, examining the distribution of individual proteins in local areas of a neuronal cell, such as dendritic spines, has been challenging presumably due to binding events that are either nonspecific or involving multiple molecules interacting together.…”