OmpA, a predominant outer membrane (OM) protein in Escherichia coli, affects virulence, adhesion, and bacterial OM integrity. However, despite more than 50 y of research, the molecular basis for the role of OmpA has remained elusive. In this study, we demonstrate that OmpA organizes the OM protein lattice and mechanically connects it to the cell wall (CW). Using gene fusions, atomic force microscopy, simulations, and microfluidics, we show that the β-barrel domain of OmpA is critical for maintaining the permeability barrier, but both the β-barrel and CW-binding domains are necessary to enhance the cell envelope's strength. OmpA integrates the compressive properties of the OM protein lattice with the tensile strength of the CW, forming a mechanically robust composite that increases overall integrity. This coupling likely underpins the ability of the entire envelope to function as a cohesive, resilient structure, critical for the survival of bacteria.
Keywords: atomic force microscopy; membrane biophysics; membrane organisation; outer membrane.