3D double network (DN) hydrogel-based metastasis tumour model

• Main Author: Yew, Eugene Jin
• Other Authors: Dalton Tay Chor Yong
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2020
• Subjects: Science::Biological sciences::Molecular biology
• Online Access: https://hdl.handle.net/10356/138778
• Institution: Nanyang Technological University

The tumour microenvironment (TME) plays a significant role in cancer progression. Compared to biochemical signals, the influence of TME-derived biomechanical cues in the regulation of invasion and cancer metastasis remains unclear. Herein, a biomimetic collagen-alginate (CoAl) interpenetrating polymer network (IPN) with tuneable mechanical properties was developed to examine the effect of matrix stiffness on MDA-MB-231 invasiveness. Stiffness of the CoAl-IPN hydrogel with storage modulus (G’) ranging from 50-300 Pa can be attained by varying the crosslinking density of the alginate network. Increasing matrix stiffness leads to a build-up of mechanical stress and/or pressure experienced by the growing MDA-MB231 tumoroids as a result of the physical confinement effect. Interestingly, upon the selective degradation of the alginate network, tumoroids originally cultured in a “stiff” (~300 Pa) microenvironment displayed higher invasiveness in 3D compared to tumoroids grown in a “soft” (~100 Pa) CoAl-IPN. Specifically, the in situ characteristic starburst invasion projection of the tumoroids in the “stiff” group was found to be 4.3- fold larger relative to the “soft” experimental group. Therefore, using the developed 3D hybrid hydrogel culture system, the novel matrix-stiffness dependent mechanopriming of cancer cell invasion was revealed.