OmpA controls order in the outer membrane and shares the mechanical load

OmpA, a predominant outer membrane protein (OMP) in Gram-negative bacteria, plays a crucial role in maintaining the integrity and functionality of the bacterial outer membrane (OM). Despite its significance in virulence, adhesion, and OM stability, the specific role of OmpA has remained unclear since its discovery 50 years ago. In this study, we demonstrate that OmpA organizes the OMP lattice and mechanically connects it to the cell wall. Using atomic force microscopy, simulations, and microfluidics, we show that while the β-barrel domain of OmpA is essential for maintaining the permeability barrier, both the β-barrel and cell wall-binding domains are necessary to enhance the cell envelope's strength. We propose that OmpA integrates the compressive properties of the OMP lattice with the tensile strength of the cell wall, forming a mechanically robust composite that enhances overall envelope integrity. This coupling likely underpins the ability of the entire envelope to function as a cohesive and resilient structure, critical for the survival and pathogenicity of Gram-negative bacteria.