Figure 6.

Compression (π-A) and inverse compressibility modulus (Cs⁻¹ = A × (dπ/dA) isotherms of POPG-POPC monolayers in the presence of 1 μM WT GsMTx4 (A), K8E (B), K15E (C), K25E (D), and K28E (E). WT (green) and control (red) curves are repeated on (B–E) for comparison. The control monolayers, only lipids, compress smoothly with no phase transition. The monolayer collapses near 41.7 ± 2.9 mN/m (n = 3). At the πB taken as 40 mN/m (48), the molecular area per lipid is 66 ± 2.9 Å². Plots of Cs⁻¹ that reflect stiffness of the monolayer are aligned on the area scale with the compression isotherms. For WT GsMTx4 (A), the Cs⁻¹ plot exhibits two characteristic minima (designated 1 and 2). The first minim takes place in the middle of the compression isotherm, whereas the second minimum reached at 60–80 Å²/molecule occurs near the monolayer-bilayer equivalence pressure (πB). The gray shading highlights the area and pressure ranges where the presence of GsMTx4 may exert physiological effects. All analogs with normal activity exhibit low Cs⁻¹ values in that region indicating a facilitated pressure-dependent exchange of the peptide between “deep” and “superficial” states in the film. In the areas marked by the asterisk (B–E), the isotherms for the less-active peptides (K15E and K25E) are elevated higher above the control monolayer curves than K8E and K28E. Instead of a second minimum or low plateau as in WT (green curves), an additional peak in Cs⁻¹ is present for K15E and K25E indicating higher stiffness and no exchange. These traits suggest tighter association of the less-active peptides with the lipid; their position in the film is not as strongly perturbed by pressure. To see this figure in color, go online.