Currently, there is an extensive inventory of peptide sequences described with antimicrobial activity in literature. The scientific community repeatedly proposes molecules of this nature as one of the solutions to the fight against infectious bacteria with multi-resistance to commercial antibiotics. However, actually there are less than 5 peptides of systemic application, unlike those developed for ectopic applications that no have high risk on tissular cells, because of no contact. On the other hand, pharmaceutical companies rarely invest in the development of antibiotics, mainly because of cost-benefit reasons, leaving the state and the health sector with this responsibility.
Although vast amount of information on antimicrobial peptides is available the exact mechanism by which these peptides have their action is not fully understood. Additionally, their negative effect on biological membranes is widely accepted by observing the perturbation and loss of cellular electrochemical gradients and homeostasis. The type of structure that is formed by the peptide inserted in the target membrane and/or the modification that these peptides generate in their target membrane has been described only in very few cases.
We study the interaction of these peptides with membranes of different lipid composition, analyzing the efficiency in their action, where the activity depends not only on the lipid composition, but also on the physical parameters that are modified in the membrane, such as fluidity, transition temperature, phase segregation to mention a few. At the same time, the degree of interaction with the lipid system of the membrane is analyzed, when the peptide is inserted, we look for changes or disturbances to the membrane in addition to the evident pore formation.
The most commonly used models consist of mixtures that emulate membranes of fungi, bacteria, mammals, and tumor cells. The objective of the work is to define the physical parameters that dominate the permissibility of insertion of peptides in one membrane with respect to another, in order to define the specificity of a peptide to certain cell types. A better understanding of the parameters that govern the interaction of these peptides with the membrane will contribute to the rational development of antimicrobial peptides. The design of peptides with activity on membranes of particular interest, such as those of pathogenic microorganisms and tumor cells (but with lower insertion efficiency in host cells or healthy tissues), is ideal for systemic application.