A mechanobiological model to study upstream cell migration guided by tensotaxis
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ORIGINAL PAPER
A mechanobiological model to study upstream cell migration guided by tensotaxis Gabriel Santos Rosalem1 · Estevam Barbosa Las Casas2 · Thiago Parente Lima3 · Libardo Andrés González‑Torres3 Received: 23 July 2019 / Accepted: 11 January 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Cell migration is a process of crucial importance for the human body. It is responsible for important processes such as wound healing and tumor metastasis. Migration may occur in response to stimuli of chemical, physical and mechanical nature occurring in the cellular microenvironment. The interstitial flow (IF) can generate mechanical stimuli in cells that influence the cell behavior and interactions of the cells with the extracellular matrix (ECM). One of the phenomena is upstream migration, which is observed in some tumors. In this work, we present a new approach to study the adherent cell migration in a porous medium using a mechanobiological model, attempting to understand if upstream migration can be generated exclusively by mechanical factors. The influence of IF on the behavior of cells and the extracellular matrix was considered. The model is based on a system of coupled nonlinear differential equations solved by the finite element method. Several simulations were performed to study the upstream cell migration and evaluate the effects of pressure, permeability, ECM stiffness and cellular concentration variations on the cell velocity. The results indicated that upstream migration can occur in the presence of mechanical stimuli generated by IF and that the tested parameters have a direct influence on the cellular velocity, especially the pressure and the permeability. Keywords Mechanobiological model · Mechanosensing · Cellular migration · Finite element method · Upstream migration · Interstitial fluid
1 Introduction Cell migration is an important biological response that governs physiological and pathological processes in the human body. Some examples of these processes are the inflammatory response, wound healing, morphogenesis and tumor metastasis (Lauffenburger and Horwitz 1996; Ananthakrishnan and Ehrlicher 2007). Cell migration deficiency is associated with anomalies and complications that can compromise short-term or long-term health of individuals. * Libardo Andrés González‑Torres [email protected] Gabriel Santos Rosalem [email protected] 1
Department of Mechanical Engineering, Federal University of Minas Gerais, Belo Horizonte, Brazil
2
Department of Structural Engineering, Federal University of Minas Gerais, Belo Horizonte, Brazil
3
Institute of Science and Technology, Federal University of Jequitinhonha and Mucuri Valleys, Diamantina, Brazil
An example is congenital brain diseases, which can be attributed to a failure in the neuronal cell migration, that causes mental disorders (Muraki and Tanigaki 2015). Therefore, understanding cell migration as an integrated and coordinated process, considering the stimuli and mechanisms involved, may help in t
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