Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 26, Pages 7041-7046Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1602789113
Keywords
hydrogel; biophysics; biomaterials; polymers; mucus
Categories
Funding
- Defense Advanced Research Projects Agency Biological Robustness in Complex Settings [HR0011-15-C-0093]
- National Science Foundation (NSF) Emerging Frontiers in Research and Innovation Award [1137089]
- NSF Graduate Research Fellowship [DGE-1144469]
- Emerging Frontiers & Multidisciplinary Activities
- Directorate For Engineering [1137089] Funding Source: National Science Foundation
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Colonic mucus is a key biological hydrogel that protects the gut from infection and physical damage and mediates host-microbe interactions and drug delivery. However, little is known about how its structure is influenced by materials it comes into contact with regularly. For example, the gut abounds in polymers such as dietary fibers or administered therapeutics, yet whether such polymers interact with the mucus hydrogel, and if so, how, remains unclear. Although several biological processes have been identified as potential regulators of mucus structure, the polymeric composition of the gut environment has been ignored. Here, we demonstrate that gut polymers do in fact regulate mucus hydrogel structure, and that polymer-mucus interactions can be described using a thermodynamic model based on Flory-Huggins solution theory. We found that both dietary and therapeutic polymers dramatically compressed murine colonic mucus ex vivo and in vivo. This behavior depended strongly on both polymer concentration and molecular weight, in agreement with the predictions of our thermodynamic model. Moreover, exposure to polymer-rich luminal fluid from germ-free mice strongly compressed the mucus hydrogel, whereas exposure to luminal fluid from specific-pathogen-free mice-whose microbiota degrade gut polymers-did not; this suggests that gut microbes modulate mucus structure by degrading polymers. These findings highlight the role of mucus as a responsive biomaterial, and reveal a mechanism of mucus restructuring that must be integrated into the design and interpretation of studies involving therapeutic polymers, dietary fibers, and fiber-degrading gut microbes.
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