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Multi-scale Mechanics of Collagen Networks: Biomechanical Basis of Matrix Remodeling in Cancer

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Multi-scale Extracellular Matrix Mechanics and Mechanobiology

Part of the book series: Studies in Mechanobiology, Tissue Engineering and Biomaterials ((SMTEB,volume 23))

Abstract

The study of fiber network structure and mechanics is key to understanding extracellular matrix (ECM) remodeling in a variety of diseases, including cancer. The tumor microenvironment, which consists of stromal cells and ECM constituents, is altered by tumor cells via biochemical and biomechanical signals in order to support cancer progression. In particular, the tumor ECM displays consistent remodeling phenotypes that have been shown to aid cancer invasion both in vivo and in vitro. In this chapter, we focus on collagen—the most abundant protein in the body that endows the ECM with its structural and mechanical properties. Hydrogels made of reconstituted collagen fibers are commonly used as ECM models to study cell-matrix interactions and cancer cell migration in vitro. Due to their hierarchical organization, collagen networks reveal complex mechanical properties at different length scales. We present a comprehensive review of the experimental and modeling techniques available to investigate the structure and multi-scale mechanics of collagen. We emphasize the nonlinear mechanical properties of collagen from monomers to fiber networks and highlight the different aspects of collagen mechanics investigated using different loading conditions. Improved methods for quantitative imaging and biomechanical modeling are continuously needed to provide a holistic understanding of collagen remodeling in response to cell-generated traction forces and to elucidate the mechanobiological pathways underlying cellular responses to biophysical cues.

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Acknowledgements

The authors gratefully acknowledge the funding agencies that supported this work: National Institute of Health grants U01 CA202123 (MHZ) and R01 HL098028 (YZ), National Science Foundation grants CMMI 1463390 and CAREER 0954825 (YZ), and Department of Defense grant W81XWH-15-1-0070 (DR).

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Ferruzzi, J., Zhang, Y., Roblyer, D., Zaman, M.H. (2020). Multi-scale Mechanics of Collagen Networks: Biomechanical Basis of Matrix Remodeling in Cancer. In: Zhang, Y. (eds) Multi-scale Extracellular Matrix Mechanics and Mechanobiology. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 23. Springer, Cham. https://doi.org/10.1007/978-3-030-20182-1_11

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