Characterization of biological hydrogel barriers

Abstract

Biological hydrogel barriers include mucus, bacterial biofilms, fungal biofilms, and others. Biofilms are polysaccharide hydrogels. Biofilms are commonly found in the lungs of cystic fibrosis patients. Cystic fibrosis (CF) patients are susceptible to these types of chronic infections because their mucus barrier is abnormal. A common bacterial infection in these patients is caused by the bacterium Pseudomonas aeruginosa. While it is found that the bacteria can infect CF patients easily, the treatment of such infections by drugs had been found to be quite inefficient due to the structure of the biofilm itself and formidable mucus barrier. Mucus is a hydrogel which protects the gastrointestinal, genitor-urinal and respiratory tracts from pathogens and external environments. In our preliminary studies, topically applied nanoparticles disrupted these hydrogel barriers and resulted in the increase in permeability to solutes. The long term goal of this proposal is to understand and quantify the effects of the interaction between nanoparticles and biological hydrogel barriers. Discovering how nanoparticles disrupt the hydrogel barriers is important for understanding the health risks. The hypothesis of this research is that nanoparticles result in disruption of the hydrogel barrier structure that leads to increased exposures to co-deposited solutes. Quantifying the structural changes and diffusivity of such solutes using different novel techniques is the central object of my thesis. Bulk Rheological studies were performed using mucin samples treated with nanoparticles. It was noticed that the viscosities showed a negative trend with regards to the nanoparticle sizes which seemed to be contradictory to Einstein’s prediction. A possible mechanism of action was explained. Multiple particle tracking was performed to quantify viscosities of nanoparticles in mucin solution. Subsequently, drug diffusion studies were performed on similar samples to provide a relationship between the nanoparticle size and the drug permeability. Atomic force microscopy was performed in liquid cell using force mode on biofilms when treated with different sized nanoparticles. Micro-elasticity of these biofilms was calculated and compared.