The dual effect of fiber density and matrix stiffness on A549 tumor multicellular migration

The tumor microenvironment features dynamic biomechanical interactions between extracellular matrix physics and tumor progression. Tumor growth compresses the supportive matrix, and the stiffness-gradient guides tumor invasion. From the mechanical perspective, the complexity of the matrix topology involving durotaxis-driven metastasis remains lacking in a comprehensive description. In this study, A549 adenocarcinoma spheroids were exposed to a stiffness-and fiber-adjusted collagen matrix to examine the influence of collective motility. Centrifugated compression on the collagen constructs was adopted to mimic the matrix deformation in response to solid tumor development. Centrifugated compression physically stiffened and condensed collagen constructs simultaneously. Cultured with A549 spheroids for 7 days, compressed collagen constructs disadvantaged spheroid expansion without the effect of tumor proliferation potency but promoted matrix metalloproteinase activity corresponding to softened rigidity. Results suggested that the fibrous structure may counterbalance the matrix stiffness-induced motility.