Escherichia coli Peptidoglycan Structure and Mechanics as Predicted by Atomic-Scale Simulations

Bacteria face the challenging requirement to maintain their shape and avoid rupture due to the high internal turgor pressure, but simultaneously permit the import and export of nutrients, chemical signals, and virulence factors. The bacterial cell wall, a mesh-like structure composed of cross-linked strands of peptidoglycan, fulfills both needs by being semi-rigid, yet sufficiently porous to allow diffusion through it. How the mechanical properties of the cell wall are determined by the molecular features and the spatial arrangement of the relatively thin strands in the larger cellular-scale structure is not known. To examine this issue, we have developed and simulated atomic-scale models of Escherichia coli cell walls in a disordered circumferential arrangement. The cell-wall models are found to possess an anisotropic elasticity, as known experimentally, arising from the orthogonal orientation of the glycan strands and of the peptide cross-links. Other features such as thickness, pore size, and disorder are also found to generally agree with experiments, further supporting the disordered circumferential model of peptidoglycan. The validated constructs illustrate how mesoscopic structure and behavior emerge naturally from the underlying atomic-scale properties and, furthermore, demonstrate the ability of all-atom simulations to reproduce a range of macroscopic observables for extended polymer meshes.Author Summary: The structure of the bacterial cell wall has been a point of controversy and contention since it was first discovered. Although the basic chemical composition of peptidoglycan, the key constituent of the cell wall, is now well established, its long-range organization is not. This dearth of information at the mesoscopic scale is a result of the inability of experimental imaging techniques to simultaneously visualize both the atomic-level detail of the peptidoglycan network and its macroscopic arrangement around the bacterium. Now, using molecular dynamics (MD) simulations, we have carefully constructed and validated models of sections of the Escherichia coli cell wall in full atomic detail. By comparing various properties of these models, including elasticity, pore size, and thickness with experiments, we can discriminate between them, resolving which best represents the native wall structure. In doing so, our study provides approaches for connecting measurements made in atomic-scale MD simulations with large-scale and even macroscopic properties.