Altering mucus rheology to "solidify" human mucus at the nanoscale.

Samuel K Lai,Justin Hanes,Richard Cone,Denis Wirtz,Ying-Ying Wang,Laurent Kreplak

doi:10.1371/journal.pone.0004294

Samuel K Lai, Justin Hanes + Show 4 more

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https://doi.org/10.1371/journal.pone.0004294

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Abstract

The ability of mucus to function as a protective barrier at mucosal surfaces rests on its viscous and elastic properties, which are not well understood at length scales relevant to pathogens and ultrafine environmental particles. Here we report that fresh, undiluted human cervicovaginal mucus (CVM) transitions from an impermeable elastic barrier to non-adhesive objects sized 1 µm and larger to a highly permeable viscoelastic liquid to non-adhesive objects smaller than 500 nm in diameter. Addition of a nonionic detergent, present in vaginal gels, lubricants and condoms, caused CVM to behave as an impermeable elastic barrier to 200 and 500 nm particles, suggesting that the dissociation of hydrophobically-bundled mucin fibers created a finer elastic mucin mesh. Surprisingly, the macroscopic viscoelasticity, which is critical to proper mucus function, was unchanged. These findings provide important insight into the nanoscale structural and barrier properties of mucus, and how the penetration of foreign particles across mucus might be inhibited.

Highlights

Mucus is a highly viscous and elastic barrier that protects mucosal surfaces by selectively trapping and shedding pathogens, toxins, and ultrafine particles [1,2,3], while allowing rapid flux of nutrients, antibodies, and cells of the mucosal immune system [4,5,6]
Using high resolution multipleparticle tracking [9,18,19,20], we observed the translational movements of hundreds of fluorescent probe beads coated with a non-mucoadhesive surface [21,22], ranging from 100 to 1,000 nm in diameter, and determined the viscoelastic barrier properties of cervicovaginal mucus (CVM) at length scales relevant to pathogens
The Brownian trajectories for 100–500 nm beads, probing distances far larger than their sizes over 20 s movies, suggest that mucus acts as a low viscosity fluid at length scales up to 500 nm (Fig. 1A–C and Videos S1, S2, S3)

Summary

Introduction

Mucus is a highly viscous and elastic barrier that protects mucosal surfaces by selectively trapping and shedding pathogens, toxins, and ultrafine particles [1,2,3], while allowing rapid flux of nutrients, antibodies, and cells of the mucosal immune system [4,5,6]. The time scale-dependent displacements of non-interacting beads allow quantitative measurements of the frequency-dependent local viscous (G0(v)) and elastic (G9(v)) forces impeding their Brownian motions [9,10,15,16]. Using high resolution multipleparticle tracking [9,18,19,20], we observed the translational movements of hundreds of fluorescent probe beads coated with a non-mucoadhesive surface [21,22], ranging from 100 to 1,000 nm in diameter, and determined the viscoelastic barrier properties of CVM at length scales relevant to pathogens.

Results

Conclusion