A Computational Characterization of Nanoscale Interactions of Biological Systems

Abstract

Treatment of biofilm infections is difficult, in part, due to the bacteria’s pathogenicity and, in part, due to biofilm’s structural resilience. Not only does a drug have to traverse the extracellular matrix, but it also has to cross membranes to be delivered to the bacterial cell. Each pathway presents a unique set of challenges. In the extracellular matrix, drugs are inhibited by networks of functional amyloid fibers, among other things. At the cellular level, drug permeation has been linked to cell membrane vibrations, which inherently depend on the composition of the membrane. Nanoparticles are a promising route for controlling biofilm growth and preventing resistance because they offer a myriad of sizes, shapes, and functional groups. In this thesis, I use molecular dynamics simulations and novel analysis methods to computationally explore the nanoscale interactions of (1) proteins, (2) membranes, and (3) nanoparticles. I characterize the structure of staphylococcal paone amyloid nanofibers, identify membrane vibrations from both eukaryotic and prokaryotic organisms, and propose interactions of chiral carbon nanoparticles with teicoplanin and phenol-soluble modulins that could be responsible for their separation by high-performance liquid chromatography and anti-biofilm capabilities, respectively. The efforts of this research have increased our understanding of nanofibers through the development of in-silico models with atomistic resolution and have helped us to screen for potential nanoparticulate candidates that could serve as biofilm manipulators.