COMPUTATIONAL BIOENGINEERING OF THE GASTROINTESTINAL TRACT

Abstract

The pathogenic potential of sodium channel related mutations of R76C and G298S in causing gastrointestinal (GI) motility disorders was computationally investigated from an electrophysiological perspective, through integrative multi-scale modelling. Models describing the wild-type and mutation-altered sodium channels, in key motility cell-types of interstitial cell of Cajal (ICC) and smooth muscle cell (SMC), were developed for investigation at higher spatial scales. A single cell model of the small intestinal SMC was developed, and together with well-established single cell gastric models of ICC and SMC, they were used to investigate effects of the mutations on cellular electrophysiology. To further study the mutations, a gastric tissue model that incorporates multiple ICC and SMC through an extended bidomain approach, with proper electrical entrainment and propagation, was created. The R76C mutation presented a greater potential than the G298S mutation in altering multi-scale electrical behaviour. An electrical disruption may change smooth muscle electromechanics and cause dysmotility.