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Modelling 3D cell motility in mechano-chemo-biology: from microfluidics to numerical simulation

Presented by: 
José Manuel García Aznar
Tuesday 15th September 2015 - 14:15 to 15:00
INI Seminar Room 1
Co-authors: Moreno-Arotzena O (Universidad de Zaragoza), Ribeiro F (IST Lisbon), Borau C (Universidad de Zaragoza)

Cell motility is essential for many morphogenetic and regenerative processes, also contributing to the development of numerous diseases, including cancer. For 2D, cell movement starts with protrusion of the cell membrane followed by the formation of new adhesions at the cell front that link the actin cytoskeleton to the extracellular matrix, generation of traction forces that move the cell forwards and disassembly of adhesions at the cell rear. Although valuable knowledge has been accumulated through analysis of various 2D models, some of these insights are not directly applicable to migration in 3D. In any case, all these processes are regulated by environmental signals from the surrounding microenvironment that allow cells to guide and regulate their directional movement. Unraveling the intrinsic mechanisms that cells use to define their migration is crucial for advancing in the development of new technologies in regenerative medicine and treatment of cancer. Due to the complexity of all these mechanisms, the combination of in-vitro models (through microfluidics-based experiments) and computational simulations provide deeper insight and quantitative predictions of the mechano-chemical interplay between cells and extracellular matrix during migration With this objective in mind, we have developed microfluidic-based studies of individual 3D fibroblast movement in biomimetic microenvironments provided by the matrix and the biochemical factors that are moving in the medium. In particular, we have confined two physiologically relevant hydrogels (collagen and fibrin) in combination with two growth factors (PDGF-BB and TGF-β1). Meanwhile, we are developing novel numerical approaches that combine discrete and continuous numerical approaches in order to simulate this 3D cell migration. So, in this work, I will show recent progress that we have made in the development of different integrative numerical strategies for advancing in the simulation of cell movement in 3D
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University of Cambridge Research Councils UK
    Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons