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Cell – extracellular matrix interaction in glioma growth. In silico model

ABSTRACT: Abstract The study aims to investigate the role of viscoelastic interactions between cells and extracellular matrix (ECM) in avascular tumor growth. Computer simulations of glioma multicellular tumor spheroid (MTS) growth are being carried out for various conditions. The calculations are based on a continuous model, which simulates oxygen transport into MTS; transitions between three cell phenotypes, cell transport, conditioned by hydrostatic forces in cell–ECM composite system, cell motility and cell adhesion. Visco-elastic cell aggregation and elastic ECM scaffold represent two compressible constituents of the composite. Cell–ECM interactions form a Transition Layer on the spheroid surface, where mechanical characteristics of tumor undergo rapid transition. This layer facilitates tumor progression to a great extent. The study demonstrates strong effects of ECM stiffness, mechanical deformations of the matrix and cell–cell adhesion on tumor progression. The simulations show in particular that at certain, rather high degrees of matrix stiffness a formation of distant multicellular clusters takes place, while at further increase of ECM stiffness subtumors do not form. The model also illustrates to what extent mere mechanical properties of cell–ECM system may contribute into variations of glioma invasion scenarios.

SUBMITTER: Kalinin V

PROVIDER: S-EPMC7849632 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Project description:Mechanical interactions during angiogenesis, i.e., traction applied by neovessels to the extracellular matrix and the corresponding deformation, are important regulators of growth and neovascularization. We have previously designed, implemented, and validated a coupled model of angiogenesis in which a discrete microvessel growth model interacts with a continuous finite element mesh through the application of local remodeling sprout stresses (Edgar et al. in Biomech Model Mechanobiol, 2014). However, the initial implementation of this framework does not take matrix density into account when determined these remodeling stresses and is therefore insufficient for the study of angiogenesis within heterogeneous matrix environments such as those found in vivo. The objective of this study was to implement sensitivity to matrix density in the active stress generation within AngioFE in order to allow the study of angiogenic growth within a heterogeneous density environment. We accomplished this by scaling active sprout stresses relative to local matrix density using a scaling factor previously determined from experimental data. We then exercised the new functionality of the model by simulating angiogenesis within four different scenarios: homogeneous density, a narrow gap model, and matrix density gradient, and a construct subjected to repeated loading/unloading and preconditioning. These numerical experiments predicted heterogeneous matrix density in the initially homogeneous case, the closure and alignment of microvessels along a low-density gap, the formation of a unique cap-like structure during angiogenesis within a density gradient, and the alignment of microvessels in the absence of applied load due to preconditioning. The result of these in silico investigations demonstrate how matrix heterogeneity affects neovascularization and matrix deformation and provides a platform for studying angiogenesis in complicated and multi-faceted mechanical environments that microvessels experience in vivo.

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Cell – extracellular matrix interaction in glioma growth. In silico model

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