title: Structural biology response of a collagen hydrogel synthetic extracellular matrix with embedded human fibroblast: computational and experimental analysis.
abstract: Adherent cells exert contractile forces which play an important role in the spatial organization of the extracellular matrix (ECM). Due to these forces, the substrate experiments a volume reduction leading to a characteristic shape. ECM contraction is a key process in many biological processes such as embryogenesis, morphogenesis and wound healing. However, little is known about the specific parameters that control this process. With this aim, we present a 3D computational model able to predict the contraction process of a hydrogel matrix due to cell-substrate mechanical interaction. It considers cell-generated forces, substrate deformation, ECM density, cellular migration and proliferation. The model also predicts the cellular spatial distribution and concentration needed to reproduce the contraction process and confirms the minimum value of cellular concentration necessary to initiate the process observed experimentally. The obtained continuum formulation has been implemented in a finite element framework. In parallel, in vitro experiments have been performed to obtain the main model parameters and to validate it. The results demonstrate that cellular forces, migration and proliferation are acting simultaneously to display the ECM contraction.
authors.affiliation: Group of Structural Mechanics and Materials Modelling (GEMM), Aragón Institute of Engineering Research (13A), University of Zaragoza, Zaragoza, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Manzano
authors.forename: Raquel
authors.initials: R
authors.lastname: Moreno-Loshuertos
authors.forename: Manuel
authors.initials: M
authors.lastname: Doblaré
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ochoa
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamdy Doweidar
mesh_terms: D001696:Biomechanical Phenomena / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D019295:Computational Biology; D003470:Culture Media; D005109:Extracellular Matrix / Q000737:chemistry*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D040542:Mechanotransduction, Cellular; D008954:Models, Biological
chemical_list: D003470:Culture Media; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003094:Collagen
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