Mechanics and microstructure in biofilms and their interactions with the immune system: Why you should care, and why I think this intersection is understudied.

Biofilms are aggregates of bacteria and other microbes that are bound together in a matrix of polymer and protein. When a person develops a biofilm infection, neutrophils, a type of white blood cell, try to clear the infection. Neutrophils' initial clearance attempts are based on phagocytosis, or engulfing microbes, but they are ~10x smaller than typical aggregates in biofilm infections, so they cannot engulf the aggregate whole - if they are to clear biofilm microbes by phagocytosis, they must do so one to a few cells at a time, by extracting pathogens from the biofilm matrix and engulfing them. This is a slow, mechanically-localized process about which almost nothing is known.

We have recently found, for one important biofilm-forming human pathogen (Pseudomonas aeruginosa) growing in chronic wounds, that the biofilm's matrix composition, mechanical properties, and microstructure are sensitively dependent on both bacterial-produced matrix materials and on factors arising from growth inside an animal host, as are the efficacy of matrix-compromizing enzymatic treatments. We have also found that the success of neutrophils at engulfing constituents from a biofilm or similar target depend on the biofilm's viscoelasticity and microstructure. How these myriad parameters interplay in real-world infections, which are polymicrobial and can happen at many different anatomical sites, is not understood at all. In this talk, I will give a synthetic overview of our findings and how they point toward future investigation.