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.

细菌面临一项严苛的生理需求：既要维持自身形态、避免因较高的内部膨压而发生破裂，同时又要允许营养物质、化学信号以及毒力因子的跨膜转运。细菌细胞壁是由交联肽聚糖（peptidoglycan）链构成的网状结构，其兼具半刚性与足够的孔隙率以允许物质扩散，从而同时满足了上述两项需求。目前学界尚未明确，细胞壁的机械特性是如何由其分子特征，以及该大型细胞尺度结构中相对纤细的链的空间排布所决定的。为探究这一问题，我们构建并模拟了呈无序周向排布的大肠杆菌（Escherichia coli）细胞壁原子尺度模型。实验已知聚糖链与肽交联键呈正交取向，本研究发现该细胞壁模型具备各向异性弹性，且该特性正源于上述正交取向。厚度、孔径与结构无序性等其他特征，也普遍与实验结果相符，进一步佐证了肽聚糖的无序周向排布模型。经过验证的模型构建方式阐明了介观结构与行为如何自然地源于底层原子尺度特性，此外还证明了全原子模拟（all-atom simulations）能够复现扩展聚合物网格的一系列宏观可观测量。