MMPB Subgroup Contributed Talks

Juliana Curty Faria

CFisUC, University of Coimbra

"Fibrinogen-Mediated Erythrocyte Adhesion"

Peripheral vascular disease (PVD) is an abnormal condition of blood vessels, where they become completely or partially blocked due to atherosclerosis, which is associated with increased serum levels of fibrinogen. High levels of fibrinogen may result in increased erythrocyte aggregation, leading to changes in blood rheology. Here we combine experimental micropipette assays with mathematical modeling to gain insight into the role of fibrinogen in mediating erythrocyte adhesion. The micropipette assay permits the direct visualization of the deformation of two erythrocytes as a function of fibrinogen concentration as they adhere while being pulled apart. The computational phase-field model we implement permits us to relate the morphology of the adhered erythrocytes with the pulling force they exert on each other. By comparing the erythrocyte deformations observed in the two methodologies we are able to estimate the forces the two cells exert on each other during the micropipette assay. We further compare this value with the forces measured by AFM between fibrinogen covered spheres and erythrocytes.

Tânia Sousa

Department of Life Sciences University of Coimbra, Coimbra, Portugal

"How far can hydrogen peroxide travel in microcirculation?"

In response to a mechanical or other stimuli, vascular endothelial cells release superoxide to the extracellular medium. Part of this superoxide is readily dismutated into hydrogen peroxide, which can act as an autocrine and/or a paracrine signalling agent. In this work we developed a computer simulation to quantify the restrictions of hydrogen peroxide signalling in capillaries and arterioles. This computer simulation considered the following processes: the superoxide dismutation; the superoxide/hydrogen peroxide release by endothelial cells and uptake by erythrocytes and endothelial cells; and the diffusion and transport of hydrogen peroxide/superoxide by the blood flow. It is assumed that superoxide is produced in a ring of endothelial cells with 20μm length. For plausible cellular rates of superoxide production, local hydrogen peroxide concentrations in blood plasma may reach ~0.1 μM. Maximal concentrations occur within 10 μm and 500μm of the start of the superoxide production domains, in capillaries and arterioles, respectively. We conclude that (i) signalling through superoxide/hydrogen peroxide release to the circulation can only be autocrine in the case of the capillaries and may be paracrine in arterioles; (ii) hypothetical signalling mechanisms must be sensitive to sub-μM extracellular hydrogen peroxide concentrations, which requires peroxiredoxins or peroxidases acting as hydrogen peroxide receptors.

Gustavo Taiji Naozuka

Laboratório Nacional de Computação Científica

"Discovery of a dynamical system from simulated tumor growth data of a hybrid multiscale model"

Data-driven methods via machine learning have been useful for predicting the behavior of several complex systems in science and engineering. Recently, the Sparse Identification of Nonlinear Dynamical Systems (SINDy) method has been proposed to discover underlying governing equations from measurement data. This approach assumes that most physical systems have only a few relevant terms to the dynamics and depends on determining the best value for a threshold parameter, which eliminates non-important terms of the governing equations. However, this choice needs to be performed exhaustively, evaluating the Pareto frontier that balances model complexity and accuracy. On the other hand, sensitivity analysis (SA) is a technique that allows ranking the importance of the parameters with respect to the quantity of interest. In this work, we modify the original SINDy implementation replacing the definition of the threshold parameter with a sensitivity analysis method. The SINDy-SA method is applied to capture the dynamical system from time evolution data of different tumor phenotypes. The data are collected from a simulation of a hybrid multiscale model for tumor growth. Besides retrieving the governing equations from data, the proposed approach is automated and able to reduce high complexity models to low complexity systems of ordinary differential equations.

Rui Travasso

CFisUC, University of Coimbra

"Adhesion modulates cell morphology and migration within dense fibrous networks"

Cell movement involves the coordination between mechanical forces, biochemical regulatory pathways and environmental cues. In particular, epithelial cancer cells have to employ mechanical strategies in order to migrate through the tissue's basement membrane and infiltrate the bloodstream during the invasion stage of metastasis. In this work we explore how mechanical interactions such as spatial restriction and adhesion affect migration of a self-propelled droplet in dense fibrous media. We have performed a systematic analysis using the phase-field model and a vertex model, and we propose a novel approach to simulate cell migration with dissipative particle dynamics modelling. With this purpose we have measured in our simulation the cell's velocity and quantified its morphology as a function of the fibre density and of its adhesiveness to the matrix fibres. Furthermore, we have compared our results to a previous in vitro migration assay of fibrosarcoma cells in fibrous matrices. Our results indicate that adhesiveness is critical for cell migration, by modulating cell morphology in crowded environments and by enhancing cell velocity. In addition, we explore the morphology of epithelial tissues after multiple events of cell extrusion.