Structural repair of mechanical defects in the Mycobacterium tuberculosis outer membrane. A molecular dynamics study

The outer membrane of Mycobacterium tuberculosis plays a key role in the pathogen's resistance to environmental stress and antibiotic treatment. The structural defects of the membrane are considered as one of key potential pathways for the penetration of large molecules into the mycobacterium cell. Thus, understanding the molecular mechanisms underlying the formation and repair of defects in this membrane is important for the development of drugs with better efficacy and penetrating ability against Mycobacterium tuberculosis. In this work we used molecular dynamics simulations based on the coarse-grained Dry Martini force field to study the dynamics of membrane defect repair. The defect closing times strongly depend on their type, size, and system temperature. The fastest closing process was found for small circular holes of 3 nm diameter, which occurred within ∼1 ns at 300 K, while increasing the defect size to 6 nm resulted in closing within ∼20 ns. For the vertical fault defects, a critical height value of ∼4.85 nm was found, above which the defect closing becomes unlikely or impossible, which may determine the limitation of the membrane's ability to recover from severe mechanical damage.