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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, noncovalent, 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 nm spatial and 1 ns 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 nonswellable, 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 postprocess the LAMMPS simulated data sets 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.

 

The recent COVID-19 pandemic has propelled the field of aerosol science to the forefront, particularly the central role of virus-laden respiratory droplets and aerosols. The pandemic has also highlighted the critical need, and value for, an information bridge between epidemiological models (that inform policymakers to develop public health responses) and within-host models (that inform the public and health care providers how individuals develop respiratory infections). Here, we review existing data and models of generation of respiratory droplets and aerosols, their exhalation and inhalation, and the fate of infectious droplet transport and deposition throughout the respiratory tract. We then articulate how aerosol transport modeling can serve as a bridge between and guide calibration of within-host and epidemiological models, forming a comprehensive tool to formulate and test hypotheses about respiratory tract exposure and infection within and between individuals.