Characterization of 3D matrix conditions for cancer cell migration with elasticity/porosity-independent tunable microfiber gels

Abstract

The mechanics and architectures of the extracellular matrix (ECM) critically influence 3D cell migration processes, such as cancer cell invasion and metastasis. Understanding the roles of mechanical and structural factors in the ECM could provide an essential basis for cancer treatment. However, it is generally difficult to independently characterize these roles due to the coupled changes in these factors in conventional ECM model systems. In this study, to solve this problem, we developed elasticity/porosity-tunable electrospun fibrous gel matrices composed of photocrosslinked gelatinous microfibers (nanometer-scale-crosslinked chemical gels) with well-regulated bonding (tens-of-micron-scale fiber-bonded gels). This system enables independent modulation of microscopic fiber elasticity and matrix porosity, i.e., the mechanical and structural conditions of the ECM. The elasticity of fibers was tuned with photocrosslinking conditions. The porosity was regulated by changing the degree of interfiber bonding. The influences of these factors of the fibrous gel matrix on the motility of MDA-MB-231 tumorigenic cells and MCF-10A nontumorigenic cells were quantitatively investigated. MDA-MB-231 cells showed the highest degree of MMP-independent invasion into the matrix composed of fibers with a Young’s modulus of 20 kPa and a low degree of interfiber bonding, while MCF-10A cells did not show invasive behavior under the same matrix conditions. To understand the roles of mechanical and structural factors in the extracellular matrix on cancer cell migration, elasticity/porosity-tunable gel matrices of gelatinous microfibers were developed. The elasticity of fibers and the porosity of matrix were tuned with photocrosslinking conditions and degree of interfiber bonding, respectively. Highly malignant MDA-MB-231 cells showed the highest degree of MMP-independent invasion into the matrix composed of fibers with a Young’s modulus of 20 kPa and a low degree of interfiber bonding, while nontumorigenic MCF-10A cells did not show invasive behavior under the same matrix conditions.