Mucus clearance is the primary defense
mechanism that protects airways from inhaled infectious and toxic agents. In
the current Gel-on-Liquid mucus clearance model mucus gel is propelled on top
of a “watery” periciliary layer surrounding the cilia. However,
this model fails to explain the formation of distinct mucus layer in health or
why mucus clearance fails in disease. We propose a Gel-on-Brush model in which
layer is occupied by membrane spanning mucins and mucopolysaccharides densely tethered to the airway surface.
This brush prevents mucus penetration into the periciliary space and causes mucus to form a
distinct layer. The relative osmotic moduli of the mucus and periciliary
brush layers explain both the stability of mucus clearance in health and its
failure in airway disease.
Illustration of the airway epithelial cell
surface. The airway surface is lined by arrays of 7 micrometer
long and 200 nanometer diameter cylindrical cilia (yellow projections). In our
publication in August 24, 2012 issue of Science, it is shown that the cilia and
airway surface are covered by tethered bio-macromolecules (blue hairs) that
form dense brush-like structures. This epithelial brush protects the airways
from infectious agents and ensures efficient flow of mucus from healthy lungs.