Assembly and bactericidal mechanisms of the MAC. (a) Newly formed C5b reacts with C6 to form the stable C5b6 complex. Binding of C7 results in a hydrophobic complex that targets the membrane (mC5b-7). Membrane insertion is initiated upon binding of C8 (C5b-8) after which 12–18 copies of C9 polymerize to form the pore-forming ring structure (MAC). (b) Several hypotheses for MAC-mediated killing of Gram-negative bacteria. Model A: the MAC simultaneously disrupts the OM and IM via insertion into e.g. Bayer's junctions. Model B: the MAC or its precursors (C5b-8 or C5b-9_n) rupture the OM, which allows passage of C5b-9 components (creating another MAC), C9 alone (or fragments of C9), or other factors into the periplasm to disrupt IM integrity. This process may require additional enzymes to breakdown the PG layer.