Figure 3.

Schematic representation of free lipids in the aqueous phase, interacting with phospholipid large unilamellar vesicles (LUVs) having different critical micellar concentrations (CMCs). In the aqueous phase containing lipids and proteins, three simultaneous and competing equilibria should be considered, lipid–lipid (equilibrium constant of K₂), protein–protein (equilibrium constant of K₃), and lipid–protein (equilibrium constant of K₁) complex equilibria. Fixed protein concentration and high phospholipid concentration favor lipid–protein complex formation. In the presence of high CMC phospholipids (short hydrocarbon tails), hIAPP form a lipid–protein complex, penetrate the membranes by forming ion-like pores and do not form fibrils. hIAPP in the presence of low CMC phospholipids do not form lipid–protein complexes, and only a detergent-like mechanism is detected [128].