Resilience of three-dimensional sinusoidal networks in liver tissue

TL;DR

This study investigates the structural and functional resilience of 3D sinusoidal microvasculature networks in liver tissue, revealing their topology, anisotropic transport properties, and vulnerability to targeted damage.

Contribution

The paper introduces a novel network generation algorithm and analyzes the resilience and transport properties of liver sinusoidal networks using high-resolution imaging and modeling.

Findings

Sinusoidal networks are sub-graphs of Delaunay graphs and contain minimum spanning trees.

Transport in the networks is anisotropic, correlated with nematic order.

Networks are resilient to random damage but vulnerable to removal of high-current edges.

Abstract

Can three-dimensional, microvasculature networks still ensure blood supply if individual links fail? We address this question in the sinusoidal network, a plexus-like microvasculature network, which transports nutrient-rich blood to every hepatocyte in liver tissue, by building on recent advances in high-resolution imaging and digital reconstruction of adult mice liver tissue. We find that the topology of the three-dimensional sinusoidal network reflects its two design requirements of a space-filling network that connects all hepatocytes, while using shortest transport routes: sinusoidal networks are sub-graphs of the Delaunay graph of their set of branching points, and also contain the corresponding minimum spanning tree, both to good approximation. To overcome the spatial limitations of experimental samples and generate arbitrarily-sized networks, we developed a network generation algorithm that reproduces the statistical features of 0.3-mm-sized samples of sinusoidal networks, using multi-objective optimization for node degree and edge length distribution. Nematic order in these simulated networks implies anisotropic transport properties, characterized by an empirical linear relation between a nematic order parameter and the anisotropy of the permeability tensor. Under the assumption that all sinusoid tubes have a constant and equal flow resistance, we predict that the distribution of currents in the network is very inhomogeneous, with a small number of edges carrying a substantial part of the flow. We quantify network resilience in terms of a permeability-at-risk, i.e.\ permeability as function of the fraction of removed edges. We find that sinusoidal networks are resilient to random removal of edges, but vulnerable to the removal of high-current edges. Our findings suggest the existence of a mechanism counteracting flow inhomogeneity to balance metabolic load on the liver.