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. 2012 Jan 18;102(2):195-200.
doi: 10.1016/j.bpj.2011.11.4010.

Coarse-grained modeling of mucus barrier properties

Pawel Gniewek  1 , Andrzej Kolinski
Affiliations

Coarse-grained modeling of mucus barrier properties

Pawel Gniewek et al. Biophys J. .

Abstract

We designed a simple coarse-grained model of the glycocalyx layer, or adhesive mucus layer (AML), covered by mucus gel (luminal mucus layer) using a polymer lattice model and stochastic sampling (replica exchange Monte Carlo) for canonical ensemble simulations. We assumed that mucin MUC16 is responsible for the structural properties of the AML. Other mucins that are much smaller in size and less relevant for layer structure formation were not included. We further assumed that the system was in quasi-equilibrium. For systems with surface coverage and concentrations of model mucins mimicking physiological conditions, we determined the equilibrium distribution of inert nanoparticles within the mucus layers using an efficient replica exchange Monte Carlo sampling procedure. The results show that the two mucus layers penetrate each other only marginally, and the bilayer imposes a strong barrier for nanoparticles, with the AML layer playing a crucial role in the mucus barrier.

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Figures

Figure 1
Figure 1
Elementary moves employed in the stochastic dynamics of model mucin chains.
Figure 2
Figure 2
Snapshot from REMC simulations of the mucus/nanoparticles system. Black: nanoparticles. Purple and blue: MUC16 A and B domains, respectively. Red and green: polar and hydrophobic domains of LML mucins, respectively.
Figure 3
Figure 3
Distributions of the end-to-end vectors of the MUC16 brush for various surface densities of the anchor M domains.
Figure 4
Figure 4
Distribution of A domains (purple), B domains (blue), and nanoparticles (black) for the AML layer (not covered by the gel layer) for the system with surface coverage equal to 0.05. For better readability, the scale for nanoparticle distribution is given at the right-hand side of the plot.
Figure 5
Figure 5
Distribution of nanoparticles density for the AML layer (not covered by the gel layer) for various surface coverage. The leftmost points of distributions correspond to nanoparticles. touching the membrane surface.
Figure 6
Figure 6
(A) Distribution of MUC16 segments and across the AML/LML mucus layer (for better readability, the scale for nanoparticle distribution is given at the right-hand side of the plot). (B) The corresponding distribution of the gel mucins.
Figure 7
Figure 7
Density profiles of the MUC16 B domains in the presence and absence of LML.
See this image and copyright information in PMC

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