α2-Adrenergic receptors belong to a large family of membrane proteins, known as G-protein coupled receptors (GPCRs), involved in signalling across biological membranes. The association of GPCRs to the plasma membrane makes them susceptible to their lipid environment and in turn, these proteins are also capable of modulating the lipid structure and properties of the membranes with which they interact. To study peptide-lipid interactions, model peptides consisting of a simple repeating motif designed to form stable α-helices have been the most common approach used [1]. Our experimental design followed a novel strategy using peptides with identical sequences to the putative transmembrane segments (TM), H4, H6 and H7 helix, of the human α2-adrenergic receptor subtype C10 (P08913). P6 peptide contains the hydrophobic and the hydrophilic terminal sequence of the full TMH segment (H6), whereas P4 and P7 peptides only have the hydrophobic core of the transmembrane segments (TM) (H4 and H7). Molecular and structural parameters of peptide-DEPE membranes have been analyzed by fluorescence, DSC, X-ray diffraction and FTIR techniques. The study highlights the importance of the conceptual design of the peptide sequences using naturally derived aminoacid sequences when mimicking TM proteins as templates.[1] J. A. Killian, T. K. Nyholm. 2006. Curr Opin Struct Biol. 16:473-479