Role of Cancer Cells on Force Transmission in a Multicomponent, Multicell Model of the Endothelium
Mentor 1
Mahsa Dabagh
Start Date
16-4-2021 12:00 AM
Description
Circulating cancer cells (CC) impact the hemodynamics in their vicinity. Altering local hemodynamics exposed on endothelial cells (EC) will influence their gene expression and overall cellular activity, e.g., cell proliferation, cell apoptosis and migration. Previous research has shown that CCs may facilitate metastasis by exposing high shear stresses on ECs. In addition, past research has demonstrated that the stiffness of the extracellular matrix (ECM) also impacts the mechano-transduction in ECs. The objective of this study is to investigate the impact of these high shear forces, and of the stiffness of the ECM, upon inter/intra-cellular organelles of ECs. Our study will lead to elucidate the cellular organelles that facilitate transmigration to CCs, and in turn it will lead to understanding how metastasis occurs and therefore how it can be prevented. A 3D, multicomponent, multi-cell model of the EC monolayer was designed to study the impact of force transmission upon the EC components, caused by CCs. The model was designed and created using COMSOL Multiphysics CAD software. A digital monolayer of the endothelium was created, and the natural conditions found within the vasculature were simulated. The geometric model of the endothelium was developed with the ECM and the following EC components: focal adhesions, adherens junctions, stress fibers, nucleus, apical layer, glycocalyx layer and the cytoplasm. Currently, the study is at its post-processing phase. The expected results are that the stiffness of the ECM will influence the mechano-transduction in ECs. In conclusion, our findings will quantify the effects of the stiffness of the ECM upon the EC organelles, and will lead to assisting the development of an effective treatment strategy to suppress the metastasis of cancer cells.
Role of Cancer Cells on Force Transmission in a Multicomponent, Multicell Model of the Endothelium
Circulating cancer cells (CC) impact the hemodynamics in their vicinity. Altering local hemodynamics exposed on endothelial cells (EC) will influence their gene expression and overall cellular activity, e.g., cell proliferation, cell apoptosis and migration. Previous research has shown that CCs may facilitate metastasis by exposing high shear stresses on ECs. In addition, past research has demonstrated that the stiffness of the extracellular matrix (ECM) also impacts the mechano-transduction in ECs. The objective of this study is to investigate the impact of these high shear forces, and of the stiffness of the ECM, upon inter/intra-cellular organelles of ECs. Our study will lead to elucidate the cellular organelles that facilitate transmigration to CCs, and in turn it will lead to understanding how metastasis occurs and therefore how it can be prevented. A 3D, multicomponent, multi-cell model of the EC monolayer was designed to study the impact of force transmission upon the EC components, caused by CCs. The model was designed and created using COMSOL Multiphysics CAD software. A digital monolayer of the endothelium was created, and the natural conditions found within the vasculature were simulated. The geometric model of the endothelium was developed with the ECM and the following EC components: focal adhesions, adherens junctions, stress fibers, nucleus, apical layer, glycocalyx layer and the cytoplasm. Currently, the study is at its post-processing phase. The expected results are that the stiffness of the ECM will influence the mechano-transduction in ECs. In conclusion, our findings will quantify the effects of the stiffness of the ECM upon the EC organelles, and will lead to assisting the development of an effective treatment strategy to suppress the metastasis of cancer cells.
