Poking and Sealing Holes: Interactions of Antimicrobial Peptides and Poloxamers with Lipid Membranes

The cell membrane acts as a barrier, controlling the transport of molecules into and out of the cell. When the structural integrity of the membrane is compromised, so does its barrier function. In this talk, we examine how the membrane barrier function can be compromised by antimicrobial peptides, and how leakage of intracellular materials from a structurally damaged cell membrane can be arrested by triblock copolymers. Antimicrobial peptide is a class of peptide innate to various organisms and function as a defense agent against harmful microorganisms by means of membrane disordering. Despite their enormous biomedical potentials, progress towards developing them into therapeutic agents has been hampered by a lack of understanding of their mechanism of action. A class triblock copolymer of the form poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)(PEO-PPO-PEO) has been shown to help seal electroporated cell membranes, arresting the leakage of intracellular materials of the damaged cell. However, the interaction mechanism between the cell membrane and poloxamer is still unclear. Using a variety of model systems and biophysical techniques, we have examined the targeting selectivity as well as the membrane disruption mechanism of antimicrobial peptide protegrin-1, and have explored the sealing capability of poloxamer 188.