Controlling the mechanical properties of three-dimensional matrices via non-enzymatic collagen glycation

Abstract

The mechanical properties of the extracellular matrix play an important role in maintaining cellular function and overall tissue homeostasis. Recently, a number of hydrogel systems have been developed to investigate the role of matrix mechanics in mediating cell behavior within three-dimensional environments. However, many of the techniques used to modify the stiffness of the matrix also alter properties that are important to cellular function including matrix density, porosity and binding site frequency, or rely on amorphous synthetic materials. In a recent publication, we described the fabrication, characterization and utilization of collagen gels that have been non-enzymatically glycated in their unpolymerized form to produce matrices of varying stiffness. Using these scaffolds, we showed that the mechanical properties of the resulting collagen gels could be increased 3-fold without significantly altering the collagen fiber architecture. Using these matrices, we found that endothelial cell spreading and outgrowth from multi-cellular spheroids changes as a function of the stiffness of the matrix. Our results demonstrate that non-enzymatic collagen glycation is a tractable technique that can be used to study the role of 3D stiffness in mediating cellular function. This commentary will review some of the current methods that are being used to modulate matrix mechanics and discuss how our recent work using non-enzymatic collagen glycation can contribute to this field.

Keywords: :

• matrix stiffness
• endothelial cell
• angiogenesis
• glycation
• biomaterials
• three-dimensional

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Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This work was supported by funding from the National Institutes of Health (GM103388 HL097296) and the Cornell Center on the Microenvironment and Metastasis through Award Number U54CA143876 from the National Cancer Institute to C.A.R. and a National Science Foundation Graduate Research Fellowship and a fellowship through the National Science Foundation Graduate STEM Fellows in K–12 Education Program to B.N.M.