Abstract
The gut is where food is digested and nutrients are absorbed, therapeutics are often delivered, and many infections take hold. The gut microbiota is in symbiosis with its host, and can influence host health and behavior. Though the gut holds these central roles, little is understood about the physics of how soft materials interact with and shape the physicochemical environment of the gut. Soft materials abound in the gut in the form of particulates (e.g., microbes, viruses, therapeutic particles, food granules) and polymers (e.g., dietary fibers, therapeutics, food additives). This thesis explores the soft matter physics of the gut and how physicochemical interactions can influence gut structure and function. This is studied through a combination of mouse experiments and numerical calculations. In the first part of this thesis, we investigate how particulates interact with polymers in the small intestine. We find that polymers from dietary fiber can aggregate particulates by a mechanism that is qualitatively consistent with depletion interactions. This mechanism is distinct from agglutination via specific chemical interactions. In the second part of this thesis, we investigate how polymers interact with the colonic mucus hydrogel. Colonic mucus is the nexus of host-microbe interactions. It is a barrier which protects against microbial infiltration, and alterations to its physical structure have been linked to changes in host health. Here, we find that polymers compress the colonic mucus hydrogel. For uncharged polymers, this mechanism can be described by a simple, mean-field model based on Flory-Huggins solution theory. Further, we find that microbes can modulate the extent of mucus compression by degrading polymers in the gut. In the last part of this thesis, we find that charged polymers (polyelectrolytes) compress mucus by a Donnan mechanism.
Item Type: | Thesis (Dissertation (Ph.D.)) |
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Subject Keywords: | Biophysics; polymers; soft matter; gut; mucus; dietary fiber; flocculation; colloids; hydrogel |
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Degree Grantor: | California Institute of Technology |
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Division: | Chemistry and Chemical Engineering |
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Major Option: | Chemistry |
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Awards: | The Herbert Newby McCoy Award, 2019. |
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Thesis Availability: | Public (worldwide access) |
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Research Advisor(s): | |
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Thesis Committee: | - Wang, Zhen-Gang (chair)
- Ismagilov, Rustem F.
- Kornfield, Julia A.
- Tirrell, David A.
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Defense Date: | 12 April 2019 |
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Funders: | Funding Agency | Grant Number |
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Defense Advanced Research Projects Agency (DARPA) | HR0011-15-C-0093 | NSF | 1137089 | NSF | DGE‐1144469 | Army Research Office (ARO) | W911NF-17-1-0402 | Jacobs Institute for Molecular Engineering for Medicine | UNSPECIFIED | Center for Environmental Microbiology Interactions | UNSPECIFIED |
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Record Number: | CaltechTHESIS:04162019-155405091 |
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Persistent URL: | https://resolver.caltech.edu/CaltechTHESIS:04162019-155405091 |
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DOI: | 10.7907/XPEZ-G864 |
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Related URLs: | |
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ORCID: | |
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Default Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. |
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ID Code: | 11474 |
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Collection: | CaltechTHESIS |
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Deposited By: |
Asher Preska Steinberg
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Deposited On: | 24 Apr 2019 22:03 |
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Last Modified: | 26 May 2021 01:46 |
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