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Molecular dynamics simulations to explore the structure and rheological properties of normal and hyperconcentrated airway mucus
Author(s) -
Ford Andrew G.,
Cao XueZheng,
Papanikolas Micah J.,
Kato Takafumi,
Boucher Richard C.,
Markovetz Matthew R.,
Hill David B.,
Freeman Ronit,
Forest Mark Gregory
Publication year - 2021
Publication title -
studies in applied mathematics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 46
eISSN - 1467-9590
pISSN - 0022-2526
DOI - 10.1111/sapm.12433
Subject(s) - mucus , mucin , molecular dynamics , chemical physics , airway , fluidics , polymer , biophysics , nanotechnology , chemistry , materials science , biological system , physics , biology , computational chemistry , composite material , biochemistry , ecology , meteorology , engineering , aerospace engineering
We develop the first molecular dynamics model of airway mucus based on the detailed physical properties and chemical structure of the predominant gel-forming mucin MUC5B. Our airway mucus model leverages the LAMMPS open-source code [https://lammps.sandia.gov], based on the statistical physics of polymers, from single molecules to networks. On top of the LAMMPS platform, the chemical structure of MUC5B is used to superimpose proximity-based, non-covalent, transient interactions within and between the specific domains of MUC5B polymers. We explore feasible ranges of hydrophobic and electrostatic interaction strengths between MUC5B domains with 9 nanometer spatial and 1 nanosecond temporal resolution. Our goal here is to propose and test a mechanistic hypothesis for a striking clinical observation with respect to airway mucus: a 10-fold increase in non-swellable, dense structures called flakes during progression of cystic fibrosis disease. Among the myriad possible effects that might promote self-organization of MUC5B networks into flake structures, we hypothesize and confirm that the clinically confirmed increase in mucin concentration, from 1.5 to 5 mg/mL, alone is sufficient to drive the structure changes observed with scanning electron microscopy images from experimental samples. We post-process the LAMMPS simulated datasets at 1.5 and 5 mg/mL, both to image the structure transition and compare with scanning electron micrographs and to show that the 3.33-fold increase in concentration induces closer proximity of interacting electrostatic and hydrophobic domains, thereby amplifying the proximity-based strength of the interactions.