The differential regulation of cell motile activity through matrix stiffness and porosity in three dimensional collagen matrices

Abstract

In three dimensional collagen matrices, cell motile activity results in collagen translocation, cell spreading and cell migration. Cells can penetrate into the matrix as well as spread and migrate along its surface. In the current studies, we quantitatively characterize collagen translocation, cell spreading and cell migration in relationship to collagen matrix stiffness and porosity. Collagen matrices prepared with 1 to 4 mg/ml collagen exhibited matrix stiffness (storage modulus measured by oscillating rheometry) increasing from 4 to 60 Pa and matrix porosity (measured by scanning electron microscopy) decreasing from 4 to 1 μm 2 . Over this collagen concentration range, the consequences of cell motile activity changed markedly. As collagen concentration increased, cells no longer were able to cause translocation of collagen fibrils. Cell migration increased and cell spreading changed from dendritic to more flattened and polarized morphology depending on location of cells within or on the surface of the matrix. Collagen translocation appeared to depend primarily on matrix stiffness, whereas cell spreading and migration were less dependent on matrix stiffness and more dependent on collagen matrix porosity.

Inelastic behaviour of collagen networks in cell–matrix interactions and mechanosensation

“…In contrast to these reports, our results show a much earlier decay in the rate of network deformation by adherent cells on dense networks. This finding may reflect higher levels of physical interactions because of the small pore size of the dense network [28].…”

“…To examine the influence of covalent cross-linking of collagen fibres on stress-relaxation and strain rate-dependent mechanics of collagen gels, we treated gels with 0.5% GA after the networks had fully polymerized [27,28]. When GA cross-linked collagen networks were subjected to cyclic loading and unloading, the rate-dependent inelastic behaviour was completely inhibited.…”

Observing and Quantifying Fibroblast-mediated Fibrin Gel Compaction

“…Adding a dilute amount of collagen can help keep the cells of the explant together. This procedure may be compared to the nested collagen matrices method developed by Grinnell et al, where cell migration and changes in collagen microstructure can also be studied by placing cell-populated collagen gels into acellular collagen gels 25,26 . Obtaining focused images throughout the experiment is also very important.…”

Controlling collagen fiber microstructure in three-dimensional hydrogels using ultrasound

“…Interestingly, the mechanical stiffness of collagen hydrogels is dependent upon collagen fiber microstructure, where thinner fibers result in stiffer gels (Roeder et al, 2002;Raub et al, 2007;Yang et al, 2009). Physical parameters of collagen gels, such as fiber density, and bulk gel stiffness affect cell proliferation, viability, differentiation, and migration (Hansen et al, 2006;Sung et al, 2009;Baker et al, 2010;Miron-Mendoza et al, 2010). Thus there has been strong interest in developing technologies that can tune the physical properties of collagen gels to control cell behavior (Cen et al, 2008).…”