Interstitial flow in the chick yolk sac exhibits organ-scale patterns driven by segregated leakage and drainage

Abstract

Interstitial flow plays a key role in drug delivery, angiogenesis, cancer, and edema. Recent studies have identified connected interstitial pathways that can transport material over long distances. However, the spatial scale of physiological interstitial flow remains unclear: despite the existence of connected pathways, flow may be dominated by nearby vascular filtration or extend over longer distances. Here, we identify organ-scale interstitial flow patterns in the chick yolk sac and elucidate the mechanisms that determine their spatial scale. The yolk sac contains an organ-scale interstitial region that enables large-scale flow patterns to be identified without truncation. Our approach combines experimental imaging with computational modeling of coupled blood and interstitial flow in the whole yolk sac. Scaling analysis identifies a hydraulic conductivity ratio that controls the transition from small-scale to organ-scale flow. In organ-scale patterns, we find interstitial flow speed to be substantially greater than the transvascular flow speed. Mechanistically, the organ-scale patterns arise from the spatial segregation of the leakage and drainage of interstitial fluid from the vessels. These findings have important implications for biological transport by interstitial flow, suggesting that flow-mediated cues may be sensed locally but generated nonlocally.