Mechanical decision trees for investigating and modulating single-cell cancer invasion dynamics

Abstract

Physical cues exist across all biological scales, from the geometries of molecules to the shapes of complex organisms. While their roles have been identified across a range of scales, i.e. the arrangements of biomolecules and the form and function of tissues, less is known in some intermediate lengths. Particularly, at the cell scale, there is emerging evidence demonstrating the impact of mechanical signals, such as substrate stiffness and confinement, on many critical biological processes and malignancies, especially cancer dissemination. In the context of cell invasion, it is currently unclear how cells select from accessible mechanical paths that result in migratory patterns observed in physiological environments. Here, we devise microchannel decision trees to explore how fundamental and ubiquitous mechanical factors, specifically dimensionality and directionality, affect migratory cell decision making. We then implement strategies based purely on mechanical asymmetries to induce repetitive, non-disseminating motions, in a phenomenon we call iteratio ad nauseam.