Peptide-Lipid Interactions

Peptide-Lipid Interactions
Author: Sidney A. Simon
Publisher: Academic Press
Total Pages: 606
Release: 2002-11-13
Genre: Science
ISBN: 0080925855

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

Biophysical Interactions of Peptides and Their Analogues with Lipid Membranes

Biophysical Interactions of Peptides and Their Analogues with Lipid Membranes
Author: Anja Stulz
Publisher:
Total Pages:
Release: 2019
Genre:
ISBN:

Abstract: Many drugs, displaying a wide range of structures and diverse applications, can cross or bind to lipid membranes. Quantitative understanding of membrane interactions is thus important for several therapeutic approaches. First, membrane permeabilization represents the dominating mode of action of antimicrobial peptides (AMPs) and their synthetic mimics (SMAMPs). In terms of clinical applications, selectivity for bacterial over mammalian membranes is as important as good activity. Second, membrane interactions might influence loading, retaining, and releasing drugs from lipid-based drug delivery systems in a time controlled and targeted manner. Understanding the binding behaviour of the peptide drug exenatide to lipid membranes is not only important for characterization of its release from vesicular phospholipid gels, but might also help to understand other complex peptide-lipid interactions. The main aim of this thesis was to derive a mechanistic understanding of interactions of peptides and their analogues with model lipid membranes with a focus on the lipid composition of a membrane. Membrane permeabilization induced by AMPs and SMAMPs was quantified by a lifetime-based leakage assay using calcein-loaded vesicles. Different leakage behaviours were identified by considering active concentrations, strengths of individual leakage events, L1, and cumulative kinetics. Further experiments using isothermal titration calorimetry (ITC), monolayer adsorption measurements, and differential scanning calorimetry (DSC) helped to characterize the initial binding of AMPs and SMAMPs to lipid membranes and their propensity to induce electrostatic lipid clustering. Leakage experiments showed that the leakage behaviour changes with both, the structure of the AMP or SMAMP and the lipid composition of the membrane. The activity seems to increase if a membrane-active agent favours a permeabilization mechanism to which the particular lipid composition is especially susceptible. A closer look at kinetic profiles allowed distinguishing leakage induced by asymmetric stress from leakage events that occur stochastically. Very hydrophobic and unselective compounds seem to act mainly by hydrophobically driven asymmetry stress, especially when acting on zwitterionic phosphatidylcholine (PC) membranes. This mechanism brings about poor selectivity because all lipid membranes (bacterial and mammalian) contain a hydrophobic core. Stochastic leakage events, on the other hand, probably depend more on lipid compositions. Negatively charged lipids like phosphatidylglycerol (PG) or cardiolipin (CL) triggered the initial electrostatic attraction of polycationic AMPs or SMAMPs to bacterial membranes. High amounts of phosphatidylethanolamine (PE) seem to counteract the unselective asymmetry stress mechanism. Finally, especially strong leakage events were induced in vesicles containing CL. In this way, compounds that induce only rare leakage events might still be effective. In the second part of the thesis, an ITC fit model was introduced to study complex peptide-lipid interactions based on primary binding of peptide to the lipid layer and secondary binding to pre-bound peptide. Exenatide served as an exemplary peptide that interacts electrostatically with mixed POPC/POPG liposomes and self-associates at Kd = 46 μM. A global fit of various ITC curves revealed that exenatide binds primarily to a binding site at the outer membrane leaflet composed of 2-3 negatively charged POPG and some POPC molecules. Primary binding showed high affinity with a Kd1 of 0.2-0.6 μM, while secondary binding with a Kd2 of 10-46 μM was weaker. ITC was able to quantify primary and secondary binding separately, based on different binding enthalpies. Unlike ITC, other methods such as tryptophan fluorescence and microscale thermophoresis (MST) probably represent only a summary or average of both effects. Many similar ITC data can be found in literature that possibly involve primary and secondary binding effects. Those data could benefit from a fit model as presented in this thesis

Membrane Protein – Lipid Interactions: Physics and Chemistry in the Bilayer

Membrane Protein – Lipid Interactions: Physics and Chemistry in the Bilayer
Author: Jordi H. Borrell
Publisher: Springer
Total Pages: 126
Release: 2016-03-15
Genre: Science
ISBN: 3319302779

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.

Peptide-Liposome Model Systems for Triggered Release

Peptide-Liposome Model Systems for Triggered Release
Author: Camilla Skyttner
Publisher: Linköping University Electronic Press
Total Pages: 94
Release: 2018-09-12
Genre:
ISBN: 9176853373

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.

Protein-Lipid Interactions

Protein-Lipid Interactions
Author: Lukas K. Tamm
Publisher: John Wiley & Sons
Total Pages: 470
Release: 2006-05-12
Genre: Science
ISBN: 3527606998

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.

Protein-Lipid Interactions

Protein-Lipid Interactions
Author: C.Reyes Mateo
Publisher: Springer
Total Pages: 0
Release: 2005-12-05
Genre: Science
ISBN: 9783540284000

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.

Investigating Peptide-lipid Interactions at Single Molecule Level

Investigating Peptide-lipid Interactions at Single Molecule Level
Author: Tina Rezaie Matin
Publisher:
Total Pages: 140
Release: 2017
Genre:
ISBN:

Despite the utmost importance of protein- lipid interactions in cellular activity, due to technical difficulties, this class of interactions has not been understood mechanistically. Obtaining a more complete understanding of these interactions would, for example, aid the design of more compatible and effective medicine to target specific cells. We developed a physical technique to study such interactions and investigated the interactions between small portions of a model protein with different types of membrane. We were able to detect physical interaction differences between the two at the single-molecule level. This technique is generalizable to study other small molecule-membrane interactions and helps scientists to have a better understanding of the transport of energy, nutrition and waste in and out of the cells. The machine that has been used in our investigations is a mechanical microscope called an AFM (atomic Force Microscope). In addition to making a topographical images, this tool enables us to pick up small molecules in a controlled and precise manner.