Mucosal Immunology

All exposed organs not covered by skin, including the respiratory, gastrointestinal and female reproductive tracts, are coated with sticky, viscoelastic mucus secretions that act as the fundamental interface separating these organs from the outside world. We rarely give it a second thought, but our bodies secrete liters of mucus each day, enabling life processes like swallowing, blinking and copulation. Mucus also plays an essential protective role, continuously trapping and filtering out foreign particulates. Trapped particulates cannot reach underlying epithelial cells, and are eventually safely eliminated along with natural mucus clearance mechanisms (e.g. ciliary beating, coughing, peristalsis).

The mucosal layer’s trapping ability is highly dependent on the size and the surface chemistry of the foreign invaders. Viruses are among the smallest microbes the human body encounters, 20-100 nm in effective radius, and have evolved to have minimal binding affinity with the network of mucin fibers in healthy mucus secretions. Because the mucus layer is so thin, 50-100 microns, the natural process of diffusion alone is sufficient for viruses to readily traverse the layer and infect underlying cells. To counter these viral threats, the human body has developed a complex array of immune mechanisms. The term mucosal immunology refers to the study of the various cellular and molecular mechanisms that are dedicated to protecting against harmful foreign pathogens.

In recent years I have been collaborating with groups headed by Sam Lai (UNC, Eshelman School of Pharmacy) and Greg Forest (UNC, Mathematics) to develop a mathematical framework to analyze the interaction of HIV virions and the human body’s first responders.

Using computational modeling to optimize the design of antibodies that trap viruses in mucus (pdf)
Timothy Wessler, Alex Chen, Scott A McKinley, Richard Cone, M Gregory Forest and Samuel K Lai. Accepted. To appear in ACS Infectious Disease (2015)

Minimizing biases associated with tracking analysis of submicron particles in heterogeneous biological fluids (pdf)
Ying-Ying Wang, Kenetta L Nunn, Dimple Harit, Scott A McKinley, and Samuel K. Lai.
Journal of Controlled Release.Vol 220, Part A, pgs 37-43 (2015)

Modeling of Virion Collisions in Cervicovaginal Mucus Reveals Limits on Agglutination as the Protective Mechanism of Secretory Immunoglobulin A (pdf)
Alex Chen, Scott A McKinley, Feng Shi, Simi Wang, Peter J Mucha, Dimple Harit, M Gregory Forest, and Samuel K Lai. PLoS ONE 10(7): e0131351. doi:10.1371/journal.pone.0131351 (2015)

Modeling Neutralization Kinetics of HIV by Broadly Neutralizing Monoclonal Antibodies in Genital Secretions Coating the Cervicovaginal Mucosa. (pdfsupplemental)
Scott A McKinley, Alex Chen, Feng Shi, Simi Wang, Peter J Mucha, M Gregory Forest, Samuel K Lai. PLoS ONE 9(6): e100598. (2014) doi:10.1371/journal.pone.0100598

Transient Antibody-Mucin Interactions Produce a Dynamic Molecular Shield against Viral Invasion. (pdf)
Alex Chen, Scott A McKinley, Simi Wang, Feng Shi, Peter J. Mucha, M. Gregory Forest, & Samuel K Lai. Biophysical Journal, 106(9), 2028–2036. doi:10.1016/j.bpj.2014.02.038 (2014)