Biophysical Society Thematic Meeting | Stockholm 2022

Physical and Quantitative Approaches to Overcome Antibiotic Resistance

Poster Abstracts

21-POS Board 21 TIGHTLY PACKED: INTERROGATING CELL ENVELOPE MECHANICS WITH A PRE-STRAINED CELL WALL

David Ryoo 1 ; Hyea Hwang 1 ; James C Gumbart 1 ; 1 Georgia Institute of Technology, Atlanta, GA, USA

The cell envelope of Gram-negative bacteria acts as a physical and chemical barrier against harmful small molecules via selective diffusion. It also must withstand the turgor pressure resulting from the high concentration of solutes inside the cell. It is composed of three components: the inner membrane, the outer membrane (OM), and the peptidoglycan cell wall between them. The cell wall is connected to the outer membrane by Braun’s lipoprotein (Lpp). Previously, we determined how each component of the cell envelope responds to induced strain, concluding that most of the turgor pressure is borne by the OM and the cell wall. However, how these two components work together remains to be elucidated. Using molecular dynamics, we have simulated the combined system of the OM and the cell wall linked by multiple Lpp copies. We also constructed and simulated the system with pre-strained cell wall that was stretched 2x and 2.5x its original size to observe how the overall system adjusts, finding that the OM is resistant to the induced stress. We also calculated the area compressibility of the combined OM and cell wall system under different degrees of cell wall strain. Our results provide key insights into cell envelope stability and suggest promising directions for disrupting it.

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