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.

Alternative SiO2 Surface Direct MDCK Epithelial Behavior

“…Because we observed significant changes in the manner that the MDCK cells interact with their substrate as well as with each other, we tested whether there was differential protein adsorption, specifically ECM protein adsorption to these different surfaces. The ECM is a complex material that is secreted from cells in the case of an epithelium; this matrix is often found on the basal lateral face. , The ECM serves as a substrate for the growth and maintenance of epithelial cells as well as serving as a bulletin board for guidance cues and signals for migrating cells . The ECM is composed of several major families of proteins, including collagens, laminins, and fibronectin.…”

“…On the basis of the protein adsorption results above, we need to clarify whether the MDCK cells may also respond to the subtle surface features through altered adhesion by remodeling their ECM as a response to the substrate because this type of response to changes in adhesive state and mechanical environment has been documented previously in a broad range of cell types. ,,,− To determine the ECM protein expression, we examined the expression of several ECM proteins in these cells, including collagen II, s-laminin, fibronectin, and collagenase using confocal microscopy and immunofluorescence. In each case, we observed an increase in ECM protein expression in MDCK cells cultured on ⟨100⟩ substrates with the most dramatic increase in the expression in collagenase (Figure ), indicating that high adhesive ability of ⟨100⟩ substrates (low ECM protein adsorption property) results in highly efficient ECM protein expression due to remodeling of ECM as a response to the ⟨100⟩ substrates.…”

“…42,43 The ECM serves as a substrate for the growth and maintenance of epithelial cells as well as serving as a bulletin board for guidance cues and signals for migrating cells. 44 The ECM is composed of several major families of proteins, including collagens, laminins, and fibronectin. To determine whether ECM proteins interact with the different SiO 2 substrates, we evaluated the adsorption of purified ECM proteins (collagen II, s-laminin, and fibronectin) using a chemiluminescent surface analysis of ECM protein adsorption, an AFM-based technique, and fluorescently labeled proteins.…”

Smart hydrogels for 3D bioprinting

“…At the current stage, computational models have been set up to assess hydrogel contraction and deformation due to cellular events such as migration, proliferation and traction, cellular concentration and distribution [98,99] . These models demonstrate the interaction between cells and materials, and quantify and correlate cellular events with engineered microenvironments [100] .…”

Skin Mechanobiology and Biomechanics: From Homeostasis to Wound Healing

“…The first observations regarding the mechanobiology of fibroblasts refer to 1983 when Allen and Schor detected the contraction of free-floating collagen gels loaded with dermal fibroblasts [127,128]. In the absence of gel anchorage (no mechanical loading), the contractile tension existing between dermal fibroblasts and collagen gels becomes unbalanced prevailing fibroblasts traction forces that lead to gel contraction.…”