Deciphering the Mechanics of Cancer Spheroid Growth in 3D Environments through Microfluidics Driven Mechanical Actuation.

Uncontrolled growth of tumor cells is a key contributor to cancer associated mortalities. Tumor growth is a biomechanical process whereby the cancer cells displace the surrounding matrix that provides mechanical resistance to the growing cells. The process of tumor growth and remodeling is regulated by material properties of both the cancer cells and their surrounding matrix, yet the mechanical interdependency between the two entities is not well understood. Herein, we developed a microfluidic platform that precisely positions tumor spheroids within a hydrogel and mechanically probes the growing spheroids and surrounding matrix simultaneously. By using hydrostatic pressure to deform the spheroid-laden hydrogel along with confocal imaging and finite element analysis, we deduced the material properties of the spheroid and the matrix in situ. For spheroids embedded within soft hydrogels, we detected decreases in the Young's modulus of the matrix at discrete locations accompanied by localized tumor growth. Contrastingly, spheroids within stiff hydrogels did not significantly decrease the Young's modulus of the surrounding matrix, despite exhibiting growth. Spheroids in stiff matrices leveraged their high bulk modulus to grow and displayed a uniform volumetric expansion. Collectively, we established a quantitative platform and provided new insights into tumor growth within a stiff 3D environment. This article is protected by copyright. All rights reserved.