Lavoie, Josephine (2026) Computational Investigation of MUC2 Mucin Rheology and Pore Characteristics: Coarse-Grained Molecular Dynamics Simulations of a Non-Gelling Polymer Model. Masters thesis, Concordia University.
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Abstract
Mucus forms a viscoelastic barrier in the gastrointestinal tract; the gel-forming mucin MUC2 is its primary structural component. Because MUC2 is too large (∼5000 amino acids) for atomistic simulation at gelation-relevant scales, this thesis develops a coarse-grained bead-spring polymer model and computational pipeline for MUC2, building on Ford et al., to determine whether physical interactions alone can reproduce gelation or whether explicit disulfide crosslinks are required.
A large-scale parameter screening (Phase 1: 4,410 simulations across five parameter dimensions and seven concentrations) with Lennard-Jones interactions revealed that the model behaves as a viscous liquid (median tan δ = 3.1, 87.9% sol-like). An optimized production study (Phase 2: 131 simulations) confirmed liquid-like behavior (tan δ ≫1) with storage moduli G′ ≈37–174 Pa. Pore characterization yielded mean diameters of 12.5–14.1 nm; validation runs with full-length dimers produced pore sizes (mean∼274 nm) within the experimental range. An exploratory chain length study (6 to 104 beads per dimer, timescales up to∼420 µs) confirmed all conditions remain liquid-like. The model does not gel.
This result is consistent with the Parsons MUC5AC model, which achieved gelation only after incorporating stochastic disulfide bonds. The work establishes a validated computational pipeline including Green-Kubo rheology and Bhattacharya-Gubbins pore characterization, and documents two methodological pitfalls (a WCA interaction potential bug and NPT equilibration volume shifts) relevant to coarse-grained LAMMPS studies. Adding explicit disulfide crosslinks is the most important next step toward a complete MUC2 model.
| Divisions: | Concordia University > Faculty of Arts and Science > Physics |
|---|---|
| Item Type: | Thesis (Masters) |
| Authors: | Lavoie, Josephine |
| Institution: | Concordia University |
| Degree Name: | M. Sc. |
| Program: | Physics |
| Date: | 30 March 2026 |
| Thesis Supervisor(s): | Mansbach, Re |
| Keywords: | MUC2, mucin, coarse-grained, molecular dynamics, rheology, pore size, LAMMPS, Green-Kubo, polymer, gel, viscoelasticity |
| ID Code: | 996988 |
| Deposited By: | Josephine Lavoie |
| Deposited On: | 29 Jun 2026 15:15 |
| Last Modified: | 29 Jun 2026 15:15 |
| Related URLs: |
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