Capturing the Interaction Potential of Amyloidogenic Proteins

Experimentally derived static structure factors obtained for the aggregation-prone protein insulin were analyzed with a statistical mechanical model based on the Derjaguin-Landau-Verwey-Overbeek potential. The data reveal that the protein self-assembles into equilibrium clusters already at low concentrations. Furthermore, striking differences regarding interaction forces between aggregation-prone proteins such as insulin in the preaggregated regime and natively stable globular proteins are found.

Figure 1

SAXS intensity $I(Q)$ (in arbitrary units) of different concentrations of insulin [1 wt % (stars), 4 wt % (upward triangles), 10 wt % (downward triangles), 20 wt % (circles)] in water at $p\mathrm{H}$ 2. The inset shows the measured form factor $P(Q)$ of dimeric insulin.

Figure 2

(a) Experimental and calculated (full lines in black) structure factors $S(Q)$ for different insulin concentrations [1 wt % (stars), 4 wt % (upward triangles), 10 wt % (downward triangles)] at $p\mathrm{H}$ 2. (b) Experimental and calculated (full lines in black) $S(Q)$ for different concentrations of lysozyme (4 wt % (upward triangles), 10 wt % (downward triangles) in 20 mM citrate buffer at $p\mathrm{H}$ 4.6).

Figure 3

(a) SAXS intensity $I(Q)$ of different concentrations of insulin [1 wt % (stars), 4 wt % (upward triangles), 10 wt % (downward triangles), 20 wt % (circles)] in water with 100 mM NaCl at $p\mathrm{H}$ 2. (b) Experimental and calculated (full lines in black) structure factors $S(Q)$ for different concentrations of insulin [1 wt % (stars), 4 wt % (upward triangles) and 10 wt % (downward triangles)] in 100 mM NaCl at $p\mathrm{H}$ 2.

Figure 4

Total intermolecular interaction potential $V(r)$ (full lines) and its attractive part $V_Y(r)$ (dashed lines) for 4 wt % insulin in water, 20% ethanol and 100 mM NaCl at $p\mathrm{H}$ 2.