Interactions of Integrin αIIbβ3 Transmembrane-Cytoplasmic Segments with Lipids in Langmuir Monolayers: Surface, Mechanical, and Morphological Properties

Integrins are transmembrane receptors that mediate cell adhesion and signaling. They perform allosteric rearrangements to transmit external signals to intracellular regions, while intracellular signaling events can also influence their extracellular behavior. The αIIbβ3 integrin, found in human platelets, is involved in the thrombosis and hemostatic processes. Protein-lipid interactions can regulate membrane organization, influencing integrin conformational states and downstream signaling. In this study, we expressed and purified peptides comprising the transmembrane (TM), the intracellular (IC) segments and a small portion of the extracellular segments (EC) of αIIb and β3 integrin and studied the surface behavior of the pure peptides and their mixtures with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), with a mixture of the zwitterionic lipid POPC with the anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), and with 1,2-dipalmitoyl-sn-3-glycerophosphocholine (DPPC) using Langmuir monolayers and Brewster angle microscopy (BAM). The peptides formed stable monolayers at the air/water interface. Mixtures with the unsaturated lipid POPC and a mixture of POPC-POPG showed a negative deviation from ideal mixing, while the mixtures with the saturated DPPC deviated positively from ideal mixing. BAM imaging revealed that pure peptides formed a continuous network of reflective threads surrounding dark patches. In the mixtures with DPPC, the threads were fragmented, while POPC mixtures maintained the connectivity. These findings showed that these peptides from integrin αIIbβ3 have different interactions with different lipids, which could have implications for integrin activation and function in platelet membranes.