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Abstract The molecular signaling pathways that orchestrate angiogenesis have been widely studied, but the role of biophysical cues has received less attention. Interstitial flow is unavoidable in vivo, and has been shown to dramatically change the neovascular patterns, but the mechanisms by which flow regulates angiogenesis remain poorly understood. Here, we study the complex interactions between interstitial flow and the affinity for matrix binding of different chemokine isoforms. Using a computational model, we find that changing the matrix affinity of the chemokine isoform can invert the effect of interstitial flow on angiogenesis—from preferential growth in the direction of the flow when the chemokine is initially matrix-bound to preferential flow against the flow when it is unbound. Although fluid forces signal endothelial cells directly, our data suggests a mechanism for the inversion based on biotransport arguments only, and offers a potential explanation for experimental results in which interstitial flow produced preferential vessel growth with and against the flow. Our results point to a particularly intricate effect of interstitial flow on angiogenesis in the tumor microenvironment, where the vessel network geometry and the interstitial flow patterns are complex. 

Abstract The transport of meltwater through porous snow is a fundamental process in hydrology that remains poorly understood but essential for more robust predictions of how the cryosphere will respond under climate change. Here, we propose a continuum model that resolves the nonlinear coupling of preferential melt flow and the nonequilibrium thermodynamics of ice‐melt phase change at the Darcy scale. We assume that the commonly observed unstable melt infiltration is due to the gravity fingering instability and capture it using the modified Richards equation, which is extended with a higher‐order term in saturation. Our model accounts for changes in porosity and the thermal budget of the snowpack caused by melt refreezing at the continuum scale, based on a mechanistic estimate of the ice‐water phase change kinetics formulated at the pore scale. We validate the model in 1D against field data and laboratory experiments of infiltration in snow and find generally good agreement. Compared to existing theory of stable melt infiltration, our 2D simulation results show that preferential infiltration delivers melt faster to deeper depths, and as a result, changes in porosity and temperature can occur at deeper parts of the snow. The simulations also capture the formation of vertical low porosity annulus known as ice pipes, which have been observed in the field but lack mechanistic understanding to date. Our results demonstrate how melt refreezing and unstable infiltration reshape the porosity structure of snow and impacts thermal and mass transport in highly nonlinear ways that are not captured by simpler models.