{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:04:09Z","timestamp":1790715849783,"version":"4.1.0"},"posted":{"date-parts":[[2026,4,20]]},"group-title":"Biophysics","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35GM147029"],"award-info":[{"award-number":["R35GM147029"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>Colonic motility disorders, including diarrhea-predominant irritable bowel syndrome and slow-transit constipation, impose a major clinical burden. Although high-resolution colonic manometry reveals characteristic spatiotemporal motor patterns, such as high-amplitude propagating contractions and cyclic motor pattern in healthy individuals, these patterns are often altered or absent in disease. Understanding how these patterns arise from underlying pacemaker, neural, and mechanical mechanisms is essential for improving treatment strategies.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We developed a biophysical whole-colon model that integrates an Interstitial Cells of Cajal\u2013inspired oscillator network, enteric nervous system reflexes, a pressure-gated modulation element motivated by rectosigmoid brake behavior, and a nonlinear tube law describing colon wall mechanics. The model simulates spatiotemporal pressure patterns along the colon and allows systematic variation of physiological parameters associated with pacemaker activity, neural reflex control, and distal gating.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A small set of parameters reproduces three illustrative motility patterns corresponding to healthy motility, diarrhea-predominant irritable bowel syndrome, and slow-transit constipation. The simulated pressure maps recapitulate key features observed in high-resolution manometry, including propagation direction, regional patterning of contractions, and case-specific changes in amplitude and coordination. Sensitivity analysis suggests that proximal excitation strength and waveform morphology strongly influence global motility metrics.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>\n                    Our study presents a simple, biophysical framework for reproducing clinically observed colonic motor patterns and exploring their disruption in disease. More broadly, the model may help interpret clinical manometry in mechanistic terms and support hypothesis-driven\n                    <jats:italic>in silico<\/jats:italic>\n                    studies of colonic motility disorders.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.15.718795","type":"posted-content","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T03:15:16Z","timestamp":1776741316000},"source":"Crossref","is-referenced-by-count":1,"title":["A Biophysical Model of Human Colonic Motor Pattern Generation in Health and Disease"],"prefix":"10.64898","author":[{"given":"Ahilan Anantha","family":"Krishnan","sequence":"first","affiliation":[{"name":"Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, 46556, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil G.","family":"Dinning","sequence":"additional","affiliation":[{"name":"Department of Surgery, Flinders Medical Centre, Bedford Park, 5042, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Holland","sequence":"additional","affiliation":[{"name":"Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, 46556, IN, USA"},{"name":"Bioengineering Graduate Program, University of Notre Dame, Notre Dame, 46556, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"8","key":"2026042212301144000_2026.04.15.718795v1.1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41575-020-0286-8","article-title":"Global burden of irritable bowel syndrome: trends, predictions and risk factors","volume":"17","year":"2020","journal-title":"Nature reviews Gastroenterology & hepatology"},{"key":"2026042212301144000_2026.04.15.718795v1.2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.04.014"},{"issue":"8","key":"2026042212301144000_2026.04.15.718795v1.3","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/S2468-1253(21)00111-4","article-title":"Global prevalence of functional constipation according to the rome criteria: a systematic review and meta-analysis","volume":"6","year":"2021","journal-title":"The Lancet Gastroenterology & Hepatology"},{"key":"2026042212301144000_2026.04.15.718795v1.4","doi-asserted-by":"crossref","unstructured":"Nag, A. , Martin, S.A. , Mladsi, D. , Olayinka-Amao, O. , Purser, M. , Vekaria, R.M. : The humanistic and economic burden of chronic idiopathic constipation in the usa: a systematic literature review. 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