Cohen Lab Research

Slithering Through Slime: Mechanisms of Microbial and Molecular Motion in Mucus

Jennifer Hou

Mucus is a hydrogel secretion that lines epithelial cells in the respiratory, gastrointestinal, and urogenital tracts. The mucosal lining serves as a physical barrier against invading pathogens. We want to understand the mechanisms by which pathogenic bacteria break through this line of defense. Our hypothesis is that asymmetric secretion of proteases leads to asymmetric degradation of the surrounding protein gel. This asymmetry causes an imbalance of forces from the gel on the bacteria, which leads to motility in the direction of protease secretion.

We are currently investigating protease-powered propulsion in mucus via several means:

  • Nano- and microscopic diffusion in mucus
  • Motion induced by protease gradients
  • Fabrication of Janus particles as models of bacteria with asymmetric protease secretion

1. Diffusion in mucus:

The primary determinant of the rheology of mucus is mucin, a family of large, heavily glycosylated proteins that form a crosslinked and entangled gel of fibers. To understand motion through this mucosal environment, we study the motion of mucin molecules and beads through purified porcine gastic mucin gel.

2. Motion induced by protease gradients:

We expose a mucin gel with embedded beads to a steep protease concentration gradient and watched the beads move in this gradient. Stroboscopic trajectories of 4 micron beads moving in 1% pH 7 mucin gel over 90 minutes are shown above. Motion is induced by asymmetric degradation of the mucin environment by the proteinase K gradient.

3. Fabrication of Janus particles:

Another direction we are pursuing is to model bacteria with beads coated asymmetrically with protease. We then want to track the correlation between orientation and motion of the beads in mucus gel.




©2012 Adam E. Cohen