Tissue failure propagation as mediated by circulatory flow

Aging is driven by subcellular processes that are relatively well-understood. However the qualitative mechanisms and quantitative dynamics of how these micro-level failures cascade to a macro-level catastrophe in a tissue or organs remain largely unexplored. Here we experimentally and theoretically study how cell failure propagates in a synthetic tissue in the presence of advective flow. We argue that cells secrete cooperative factors, thereby forming a network of interdependence governed by diffusion and flow, which fails with a propagating front parallel to advective circulation. SIGNIFICANCEMortality rates typically increase for complex organisms as they age. This leads us to suggest that aging depends on interactions between cells. As cells become damaged, the effect propagates to other cells, eventually leading to a systemic catastrophe. Yet it is unclear how this failure dynamically propagates. Here we present experiments with synthetic tissues and analogous analytical models to investigate the dynamics of failure propagation. Our main contribution is a detailed investigation of failure propagation when interactions are mediated by advective flow. We find analytical expressions for when a pronounced propagation occurs, its velocity, and acceleration in terms of system parameters.