Using simulations to investigate the mechanical properties of peptidoglycan

In bacteria, the peptidoglycan (PG) cell wall counteracts the internal turgor pressure and maintains cell shape. PG consists of a mesh of glycan strands crosslinked by short peptides. Maintaining the integrity of this PG mesh is necessary to prevent cell lysis; indeed, many antibiotics target PG synthesis. The mechanical properties of the PG mesh are important for understanding the biophysics of cell growth, cell shape and antibiotic action: yet these properties are hard to measure experimentally.

Here, we present a coarse-grained molecular simulation model for the PG mesh in Gram negative bacteria such as Escherichia coli. Inspired by previous works [1,2], we model PG as a network of beads and springs governed by a system of overdamped Langevin equations. However, our model is novel in that it incorporates real configurations of glycan strands, informed by AFM and biochemical measurements.

We use dynamical simulations to study how a patch of PG responds to mechanical and biochemical perturbations. This allows us to predict mechanical properties, such as the elastic modulus and hole size distribution, for PG under different conditions. We also predict the mechanical effects of antibiotic action via uncontrolled hydrolase enzymes, and explore the role of biophysical properties of the mesh, such as connectivity, on mechanical stability.

Our work provides a connection between the molecular-scale PG configuration and the macro-scale mechanical properties of the cell wall.

[1] KC Huang et al., PNAS 2008, [2] LT Nguyen et al., PNAS 2015