Compressive remodeling alters fluid transport properties of collagen networks - implications for tumor growth
Zaman, Muhammad H.
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Citation (published version)J. Ferruzzi, M. Sun, A. Gkousioudi, A. Pilvar, D. Roblyer, Y. Zhang, M.H. Zaman. 2019. "Compressive Remodeling Alters Fluid Transport Properties of Collagen Networks - Implications for Tumor Growth.." Sci Rep, Volume 9, Issue 1, pp. 17151 - ?. https://doi.org/10.1038/s41598-019-50268-z
Biomechanical alterations to the tumor microenvironment include accumulation of solid stresses, extracellular matrix (ECM) stiffening and increased fluid pressure in both interstitial and peri-tumoral spaces. The relationship between interstitial fluid pressurization and ECM remodeling in vascularized tumors is well characterized, while earlier biomechanical changes occurring during avascular tumor growth within the peri-tumoral ECM remain poorly understood. Type I collagen, the primary fibrous ECM constituent, bears load in tension while it buckles under compression. We hypothesized that tumor-generated compressive forces cause collagen remodeling via densification which in turn creates a barrier to convective fluid transport and may play a role in tumor progression and malignancy. To better understand this process, we characterized the structure-function relationship of collagen networks under compression both experimentally and computationally. Here we show that growth of epithelial cancers induces compressive remodeling of the ECM, documented in the literature as a TACS-2 phenotype, which represents a localized densification and tangential alignment of peri-tumoral collagen. Such compressive remodeling is caused by the unique features of collagen network mechanics, such as fiber buckling and cross-link rupture, and reduces the overall hydraulic permeability of the matrix.
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