Peptide Lipid Interactions

This volume contains a comprehensive overview of peptide-lipid interactions by leading researchers. The first part covers theoretical concepts, experimental considerations, and thermodynamics. The second part presents new results obtained through site-directed EPR, electron microscopy, NMR, isothermal calorimetry, and fluorescence quenching. The final part covers problems of biological interest, including signal transduction, membrane transport, fusion, and adhesion. Key Features * world-renowned experts * state-of-the-art experimental methods * monolayers, bilayers, biological membranes * theoretical aspects and computer simulations * rafts * synaptic transmission * membrane fusion * signal transduction

Biological membranes have long been identified as key elements in a wide variety of cellular processes including cell defense communication, photosynthesis, signal transduction, and motility; thus they emerge as primary targets in both basic and applied research. This book brings together in a single volume the most recent views of experts in the area of protein–lipid interactions, providing an overview of the advances that have been achieved in the field in recent years, from very basic aspects to specialized technological applications. Topics include the application of X-ray and neutron diffraction, infrared and fluorescence spectroscopy, and high-resolution NMR to the understanding of the specific interactions between lipids and proteins within biological membranes, their structural relationships, and the implications for the biological functions that they mediate. Also covered in this volume are the insertion of proteins and peptides into the membrane and the concomitant formation of definite lipid domains within the membrane.

This book has been conceives as a brief introduction to biomembranes physical chemistry for undergraduate students of sciences, and it is particularly dedicated to the lipid-protein membrane interactions. A general introduction is presented in Chapters 1 and 2. The following Chapters, 3 and 4, describe the most accepted theories on lipid-membrane protein interactions as well as the new experimental approaches, in particular, these arose from nano sciences as atomic for microscopy and single molecule force spectroscopy. The book emphasizes the relevance of physical parameters as the lateral surface pressure and the lipid curvature as actors for understanding the physicochemical properties of the biomembranes.

Protein-lipid interactions as a field of study is now a mature area, and this volume of New Comprehensive Biochemistry has been published with two objectives in mind. Firstly, to look to the future, and try to envisage how the subject may develop in the near to medium future. Secondly, to present contrasting or complementary views on the same system. For example, the acetylcholine receptor is discussed from a predominantly structural aspect by Barrantes, and from the kinetic standpoint by Rankin, et al. The volume not only gives an update on specific aspects of the field, but also shows the way in which the phenomenon of protein-lipid interactions is now seemingly infiltrating many areas of biomembrane research, from recombinant DNA studies, protein insertion and assembly and reconstitution considerations to structural studies of membrane proteins.

In 17 contributions by leading research groups, this first comprehensive handbook in the field covers the interactions between proteins and lipids that make the fabric of biological membranes from every angle. It examines the relevant hermodynamic and structural issues from a basic science perspective, and goes on to discuss biochemical and cell biological processes. The book covers physical principles as well as mechanisms of membrane fusion and fission. Additionally, chapters on bilayer structure and protein-lipid interactions as well as on how proteins shape lipids and vice versa, membrane penetration by toxins, protein sorting, and allosteric regulation of signal transduction across membranes make this a valuable information source for researchers in academia and industry.

Liposomes are widely used in drug delivery to improve drug efficacy and to reduce side effects. For liposome-encapsulated drugs to become bioavailable and provide a therapeutic effect they must be released, which typically is a slow process that primarily relies on passive diffusion, liposome rupture or endocytotic uptake. Achieving drug concentrations within the therapeutic window can thus be challenging, resulting in poor efficacy and higher risks drug resistance. Finding means to modulate lipid membrane integrity and to trigger rapid and efficient release of liposomal cargo is thus critical to improve current and future liposomal drug delivery systems. The possibilities to tailor lipid composition and surface functionalization is vital for drug delivery applications but also make liposomes attractive model systems for studies of membrane active biomolecules. The overall aim of this thesis work has been to develop new strategies for triggering and controlling changes in lipid membrane integrity and to study the interactions of membrane active peptides with model lipid membranes using both de novo designed and biologically derived synthetic amphipathic cationic peptides. Two different sets of designed peptides have been explored that can fold and heterodimerize into a coiled coil and helix-loop-helix fourhelix bundle, respectively. Conjugation of the cationic lysine rich peptides to liposomes triggered a rapid and concentration dependent release. The additions of their corresponding glutamic acid-rich complementary peptides inhibited the release of liposomal cargo. Possibilities to reduce the inhibitory effect by both proteolytic digestion of the inhibitory peptide and by means of heterodimer exchange have been investigated. Moreover, the effects of peptide size and composition and ability to fold have been studied in order to elucidate the factors that influence the membrane permeabilizing effects of the peptides. In addition, the membrane activity of a the two-peptide bacteriocin PLNC8? and PLNC8? has been explored using liposomes as a model system. PLNC8?? are expressed by Lactobacillus plantarum and were shown to display pronounced membrane-partition folding coupling, leading to rapid release of liposome encapsulated carboxyfluorescein. PLNC8?? also kill and suppressed growth of the gram-negative bacteria Porphyromonas gingivalis by efficiently damaging the bacterial membrane. Although membrane active peptides are highly efficient in perturbing lipid membrane integrity, possibilities to trigger release using external stimuli are also of large interest for therapeutic applications. Light-induced heating of liposome encapsulated gold nanoparticles (AuNPs) has been shown by others as a potential strategy to trigger drug release. To facilitate fabrication of thermoplasmonic liposome systems we developed a simple method for synthesis of small AuNPs inside liposomes, using the liposomes as nanoscale reaction vessels. The work presented in this thesis provides new knowledge and techniques for future development of liposome-based drug delivery systems, peptide-based therapeutics and increase our understanding of peptide-lipid interactions.