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Biophys J, October 2001, p. 1930-1937, Vol. 81, No. 4

§
*Department of Biophysics, Johns Hopkins University, Baltimore,
Maryland, 21218,
Department of Obstetrics and Gynecology,
UC Davis School of Medicine, University of California-Davis,
California,
Epicyte Pharmaceutical, Inc., San Diego,
California, and §ReProtect, LLC, Baltimore, Maryland USA
To determine whether or not large macromolecules and
viruses can diffuse through mucus, we observed the motion of proteins, microspheres, and viruses in fresh samples of human cervical mucus using fluorescent recovery after photobleaching and multiple image photography. Two capsid virus-like particles, human papilloma virus (55 nm, ~20,000 kDa) and Norwalk virus (38 nm, ~10,000 kDa), as well as
most of the globular proteins tested (15-650 kDa) diffused as rapidly
in mucus as in saline. Electron microscopy of cervical mucus confirmed
that the mesh spacing between mucin fibers is large enough (20-200 nm)
for small viruses to diffuse essentially unhindered through mucus. In
contrast, herpes simplex virus (180 nm) colocalized with strands of
thick mucus, suggesting that herpes simplex virus, unlike the capsid
virus particles, makes low-affinity bonds with mucins. Polystyrene
microspheres (59-1000 nm) bound more tightly to mucins, bundling them
into thick cables. Although immunoglobulins are too small to be slowed
by the mesh spacing between mucins, diffusion by IgM was slowed by
mucus. Diffusion by IgM-Fc5µ, the Fc pentamer core of an
IgM with all 10 Fab moieties removed, was comparably slowed by
mucus. This suggests that the Fc moieties of antibodies make
low-affinity bonds with mucins.
Biophys J, October 2001, p. 1930-1937, Vol. 81, No. 4
© 2001 by the Biophysical Society 0006-3495/01/10/1930/08 $2.00
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