Computational insights into colonic motility: Mechanical role of mucus in homeostasis and inflammation

被引：0
作者：
Erbay I.H. [1 ,2 ]
Alexiadis A. [3 ]
Rochev Y. [1 ,2 ]
机构：
[1] School of Physics, University of Galway, Galway
[2] CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway
[3] School of Chemical Engineering, University of Birmingham, Birmingham
来源：
Computers in Biology and Medicine | 2024年 / 176卷
基金：
爱尔兰科学基金会; 英国工程与自然科学研究理事会;
关键词：
Computational modelling; Faecal velocity; Fluid dynamics; Inflammatory bowel disease; Intestinal motility; Mucus; Shear stress; Ulcerative colitis;
D O I：
10.1016/j.compbiomed.2024.108540
中图分类号：
学科分类号：
摘要：
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 faeces, intraluminal 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 faecal 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. © 2024
引用
收藏
相关论文
共 86 条
[1]  
Crouzier T., Boettcher K., Geonnotti A.R., Kavanaugh N.L., Hirsch J.B., Ribbeck K., Lieleg O., Modulating mucin hydration and lubrication by deglycosylation and polyethylene glycol binding, Adv. Mater. Interfac., 2, (2015)
[2]  
Abdulkarim M., Agullo N., Cattoz B., Griffiths P., Bernkop-Schnurch A., Borros S.G., Gumbleton M., Nanoparticle diffusion within intestinal mucus: three-dimensional response analysis dissecting the impact of particle surface charge, size and heterogeneity across polyelectrolyte, pegylated and viral particles, Eur. J. Pharm. Biopharm., 97, pp. 230-238, (2015)
[3]  
Ermund A., Schutte A., Johansson M.E.V., Gustafsson J.K., Hansson G.C., Studies of mucus in mouse stomach, small intestine, and colon. I. Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer's patches, Am. J. Physiol. Gastrointest. Liver Physiol., 305, pp. G341-G347, (2013)
[4]  
Atuma C., Strugala V., Allen A., Holm L., The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo, Am. J. Physiol. Gastrointest. Liver Physiol., 280, pp. G922-G929, (2001)
[5]  
Sontheimer-Phelps A., Chou D.B., Tovaglieri A., Ferrante T.C., Duckworth T., Fadel C., Frismantas V., Sutherland A.D., Jalili-Firoozinezhad S., Kasendra M., Stas E., Weaver J.C., Richmond C.A., Levy O., Prantil-Baun R., Breault D.T., Ingber D.E., Human colon-on-a-chip enables continuous in vitro analysis of colon mucus layer accumulation and physiology, Cellular and Molecular Gastroenterology and Hepatology, 9, pp. 507-526, (2020)
[6]  
Johansson M.E.V., Larsson J.M.H., Hansson G.C., The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host–microbial interactions, Proc. Natl. Acad. Sci. USA, 108, pp. 4659-4665, (2011)
[7]  
Prego C., Fabre M., Torres D., Alonso M.J., Efficacy and mechanism of action of chitosan nanocapsules for oral peptide delivery, Pharmaceut. Res., 23, pp. 549-556, (2006)
[8]  
Yao Y., Kim G., Shafer S., Chen Z., Kubo S., Ji Y., Luo J., Yang W., Perner S.P., Kanellopoulou C., Park A.Y., Jiang P., Li J., Baris S., Aydiner E.K., Ertem D., Mulder D.J., Warner N., Griffiths A.M., Topf-Olivestone C., Kori M., Werner L., Ouahed J., Field M., Liu C., Schwarz B., Bosio C.M., Ganesan S., Song J., Urlaub H., Oellerich T., Malaker S.A., Zheng L., Bertozzi C.R., Zhang Y., Matthews H., Montgomery W., Shih H.-Y., Jiang J., Jones M., Baras A., Shuldiner A., Gonzaga-Jauregui C., Snap
[9]  
Dolan B., Ermund A., Martinez-Abad B., Johansson M.E.V., Hansson G.C., Clearance of small intestinal crypts involves goblet cell mucus secretion by intracellular granule rupture and enterocyte ion transport, Sci. Signal., 15, (2022)
[10]  
Yin J., Sunuwar L., Kasendra M., Yu H., Tse C.-M., Jr C.C.T., Boronina T., Cole R., Karalis K., Donowitz M., Fluid shear stress enhances differentiation of jejunal human enteroids in Intestine-Chip, Am. J. Physiol. Gastrointest. Liver Physiol., 320, pp. G258-G271, (2021)
123456789