Diffusion of macromolecules and virus-like particles in human cervical mucus

To determine whether or not large macromolecules and viruses can diffuse th rough mucus, we observed the motion of proteins, microspheres, and viruses in fresh samples of human cervical mucus using fluorescent recovery after p hotobleaching and multiple image photography. Two capsid virus-like particl es, human papilloma virus (55 nm, similar to 20,000 kDa) and Norwalk virus (38 nm, similar to 10,000 kDa), as well as most of the globular proteins te sted (15-650 kDa) diffused as rapidly in mucus as in saline. Electron micro scopy of cervical mucus confirmed that the mesh spacing between mucin fiber s is large enough (20-200 nm) for small viruses to diffuse essentially unhi ndered through mucus. In contrast, herpes simplex virus (180 nm) colocalize d with strands of thick mucus, suggesting that herpes simplex virus, unlike the capsid virus particles, makes low-affinity bonds with mucins. Polystyr ene microspheres (59-1000 nm) bound more tightly to mucins, bundling them i nto thick cables. Although immunoglobulins are too small to be slowed by th e mesh spacing between mucins, diffusion by IgM was slowed by mucus. Diffus ion by IgM-Fc(5 mu), the Fc pentamer core of an IgM with all 10 Fab moietie s removed, was comparably slowed by mucus. This suggests that the Fc moieti es of antibodies make low-affinity bonds with mucins.