Fig. 6.

Cartoon depicting structures and bilayer forces acting on OmpA folding/unfolding under equilibrium conditions. When folding into most bilayers (left path), the process is two-state. The large black arrows indicate lateral bilayer pressure imparted on the lipid/protein interface in the hydrophobic core (red) of bilayers composed of lipids with negative intrinsic spontaneous curvature. Increasing this pressure increases the thermodynamic stability of the protein. The small black arrows indicate lipid deformation forces caused by hydrophobic mismatch between the protein and unstressed bilayers. These forces decrease the thermodynamic stability of the protein. When folding into thin bilayers (right path), the process is multistate, i.e., at least one equilibrium intermediate occurs. Water molecules penetrate more easily into the hydrophobic core (blue arrows) of more flexible and more dynamic thin bilayers, stabilizing equilibrium intermediates, decreasing the m- and values until, in very thin bilayers composed of saturated lipids, complete unfolding (second step) can no longer be observed under any of our experimental conditions.