Computational Insights into Colonic Motility: Mechanical Role of Mucus in Homeostasis and Inflammation

Abstract

Colonic motility plays a vital role in maintaining proper digestive function. The rhythmic contractions and relaxations facilitate various types of motor functions that generate both propulsive and non-propulsive motility modes which in turn generate shear stresses on the epithelial surface. However, the interplay between colonic mucus, shear stress, and epithelium remains poorly characterized. Here, we present a colonic computational model that describes the potential roles of mucus and shear stress in both homeostasis and ulcerative colitis (UC). Our model integrates several key features, including the properties of the mucus bilayer and lumen contents, colonic pressure, and crypt characteristics to predict the time-space mosaic of shear stress. We show that the mucus thickness which could vary based on the severity of UC, may significantly reduce the amount of shear stress applied to the colonic crypts and effect colonic content velocity. Our model also reveals an important spatial shear stress variance in homeostatic colonic crypts that suggests shear stress may have a modulatory role in epithelial cell migration, differentiation, apoptosis, and immune surveillance. Together, our study uncovers the rather neglected roles of mucus and shear stress in intestinal cellular processes during homeostasis and inflammation.