A generative modeling approach to connectivity-Electrical conduction in vascular networks.

The physiology of biological structures is inherently dynamic and emerges from the interaction and assembly of large collections of small entities. The extent of coupled entities complicates modeling and increases computational load. Here, microvascular networks are used to present a novel generative approach to connectivity based on the observation that biological organization is hierarchical and composed of a limited set of building blocks, i.e. a vascular network consists of blood vessels which in turn are composed by one or more cell types. Fast electrical communication is crucial to synchronize vessel tone across the vast distances within a network. We hypothesize that electrical conduction capacity is delimited by the size of vascular structures and connectivity of the network. Generation and simulation of series of dynamical models of electrical spread within vascular networks of different size and composition showed that (1) Conduction is enhanced in models harboring long and thin endothelial cells that couple preferentially along the longitudinal axis. (2) Conduction across a branch point depends on endothelial connectivity between branches. (3) Low connectivity sub-networks are more sensitive to electrical perturbations. In summary, the capacity for electrical signaling in microvascular networks is strongly shaped by the morphology and connectivity of vascular (particularly endothelial) cells. While the presented software can be used by itself or as a starting point for more sophisticated models of vascular dynamics, the generative approach can be applied to other biological systems, e.g. nervous tissue, the lymphatics, or the biliary system.