Controlling Curvature and Stiffness in Fibrous Environments Uncovers Force-Driven Processes and Phenotypes

In recent decades science has become an increasingly multidisciplinary field in which the lines that used to divide starkly different fields have blurred or disappeared completely. This work is a compendium of different angles focused at exploring disease progression of cancer biology through the perspective of mechanical engineering. We explore cancer through a holistic approach considering mechanistic, physical, genetic biology, biochemical, and immune cells to explore how the interplay with fiber networks can expand our understanding. We explored the physical interplay with biological processes of fibroblastic cells and show how these are critically regulated by forces that alter their ability to coil depends on fiber curvature and adhesion strength; thus, showing how cellular processes are driven by the balances of mechanical forces. Conversely, not all cell types are driven by the same factors, where we report that the structural features of migratory DCs enable them to be less influenced by the differences in fiber diameters, contrasting drastically what we previously reported on the other cell lines. Finally developing a novel composite nanofiber platform, we reported how some cancer cells are mechanistically influenced by the architecture of a substrate and thus resulting in completely different migratory responses that we have associated with key regulatory genes and responding completely differently when in the presence of clinically relevant molecular therapies. Overall, we investigated cancer biology through stiffness gradients, geometric influence through biophysics on myoblasts, and immune cell migration forces as a strong indicator of cell behavior.