Advances in Planar Lipid Bilayers and Liposomes

Academic Press
  • 1. Auflage
  • |
  • erschienen am 30. Juli 2015
  • |
  • 230 Seiten
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978-0-12-802910-7 (ISBN)

The Elsevier book-series Advances in Planar Lipid Bilayers and Liposomes, provides a global platform for a broad community of experimental and theoretical researchers studying cell membranes, lipid model membranes and lipid self-assemblies from the micro- to the nanoscale. Planar lipid bilayers are widely studied due to their ubiquity in nature and find their application in the formulation of biomimetic model membranes and in the design of artificial dispersion of liposomes. Moreover, lipids self-assemble into a wide range of other structures including micelles and the liquid crystalline hexagonal and cubic phases. Consensus has been reached that curved membrane phases do play an important role in nature as well, especially in dynamic processes such as vesicles fusion and cell communication. Self-assembled lipid structures have enormous potential as dynamic materials ranging from artificial lipid membranes to cell membranes, from biosensing to controlled drug delivery, from pharmaceutical formulations to novel food products to mention a few. An assortment of chapters in APLBL represents both an original research as well as comprehensives reviews written by world leading experts and young researchers.

  • The APLBL book series gives a survey on recent theoretical as well as experimental results on lipid micro and nanostructures.
  • In addition, the potential use of the basic knowledge in applications like clinically relevant diagnostic and therapeutic procedures, biotechnology, pharmaceutical engineering and food products is presented.
  • An assortment of chapters in APLBL represents both an original research as well as comprehensives reviews written by world leading experts and young researchers.
  • Englisch
  • San Diego
  • |
  • USA
Elsevier Science
  • 13,25 MB
978-0-12-802910-7 (9780128029107)
0128029102 (0128029102)
weitere Ausgaben werden ermittelt
  • Front Cover
  • Advances in Planar Lipid Bilayers and Liposomes
  • Copyright
  • Contents
  • Contributors
  • Preface
  • Chapter One: Stimuli-Sensitive Liposomes: Lipids as Gateways for Cargo Release
  • 1. Introduction
  • 2. Currently Available Nanosystems for On-Demand Cargo Release
  • 3. Triggering Solely Based on the Properties of the Lipids
  • 3.1. pH-Sensitive Liposomes
  • 3.2. Redox-Responsive Liposomes
  • 3.3. Enzyme Cleavable Liposomes
  • 3.3.1. Phospholipase A2
  • 3.3.2. Matrix Metalloproteinase MMPs
  • 3.4. Thermosensitive Liposomes
  • 3.4.1. TSL in Clinical Trials (ThermoDox)
  • 3.4.2. Cationic TSLs
  • 3.4.3. Alternate TSLs Containing Various Drugs and/or Pharmaceuticals
  • 3.4.4. Phase Transition of TSLs Modulates Efficiency of Drug Release
  • 3.4.5. Novel TSLs with Stealth Properties
  • 3.4.6. Surfactants as Destabilizing Agents in TSLs
  • 3.4.7. TSLS Bearing Tumor-Specific Ligands for Targeted Drug Delivery
  • 3.5. Phototriggerable Liposomes for On-Demand Drug Delivery
  • 3.5.1. Phototriggerable Lipids
  • 3.5.2. Phototriggering Mediated by a PS
  • 4. Clinical Status of Triggerable Liposomes and Future Considerations
  • Acknowledgments
  • References
  • Chapter Two: Effect of Lipid Bilayer Composition on Membrane Protein Association
  • 1. Introduction
  • 1.1. Role of Membrane Protein Association in Function
  • 1.2. Protein Interactions Are Suggested to Be Sequence Dependent
  • 2. Computational Methods to Analyze Association
  • 2.1. Probing the Structure of Transmembrane Dimers
  • 2.2. Calculating Dimerization Profiles of Membrane Proteins
  • 2.2.1. Unbiased Sampling Methods to Calculate Association Profiles
  • 2.2.2. Biased Sampling Methods to Calculate Association Profiles
  • 3. Association of Single Transmembrane Helices
  • 3.1. Characteristic Features of Dimerization Profiles
  • 3.2. Protein-Protein Interaction Energetics Is Similar for Wild Type and Mutants
  • 3.3. Importance of Lipid Packing and Membrane Perturbations
  • 4. GPCR Organization
  • 4.1. Effect of Membrane Composition on Organization
  • 4.1.1. Direct Membrane Effects: Cholesterol and Lipid Association
  • 4.1.2. Indirect Membrane Effects: Hydrophobic Mismatch
  • 5. A Model for Lipid-Dependent Modulation of Membrane Protein Organization
  • References
  • Chapter Three: Biomembrane Organization and Function: The Decisive Role of Ordered Lipid Domains
  • 1. Why Are Membrane Ordered Domains a Current Research Topic?
  • 2. Why Do Lipids Form Ordered Domains?
  • 3. What Is the Relevance of Planar Lipid Bilayers and Liposomes for the Study of Ordered Domains?
  • 4. How to Better Understand Ordered Domains and Their Function in Cell Membranes?
  • 4.1. Can the Diversity of Lipid Domains Be Determined?
  • 4.2. How Many Different Lipids Are Required to Mimic a Biological Membrane?
  • 4.3. In What Situations Other Biomembrane Features Should Be Comprised?
  • 5. What About Bioelectroactive Molecules and Their Redox Behavior?
  • 6. Why Study Biomembrane Ordered Domains? An Intriguing Coincidence Between In Vitro and In Vivo Studies
  • 7. Concluding Remarks
  • Acknowledgments
  • References
  • Chapter Four: Membrane-Bound Conformations of Antimicrobial Agents and Their Modes of Action
  • 1. Introduction
  • 2. Models of Antimicrobial Action
  • 3. Antimicrobial Agents with Peptide Backbone
  • 4. Antimicrobial Agents with Polymer Backbones
  • 5. Antimicrobial Polymers with Rigid Backbone
  • 5.1. Antimicrobial Polymers with Flexible Backbone
  • 6. Discussion
  • References
  • Chapter Five: Phenomenology Based Multiscale Models as Tools to Understand Cell Membrane and Organelle Morphologies
  • 1. Introduction
  • 2. Phenomenological Theories for Membranes
  • 3. Membrane Remodeling Events as Equilibrium and Nonequilibrium Processes
  • 4. Nematic Membrane Model for Protein Driven Membrane Remodeling
  • 4.1. Role of the Various Elastic Moduli
  • 4.2. Role of Nematic Density and Patterning
  • 4.3. Free Energy Methods in Nematic Membranes
  • 5. Active Membrane Models for Curvature Fluctuations
  • 6. Conclusions
  • Acknowledgments
  • References
  • Chapter Six: Membrane Microvesiculation and its Suppression
  • 1. Membrane Curvature and Cell Shape
  • 2. Membranous Nanostructures and the Fluid Crystal Mosaic Model
  • 3. Mechanisms of Micro and Nanovesiculation
  • 3.1. Budding of Plasma Membrane
  • 3.2. Budding of Internal Cell Membranes
  • 3.3. Fragmentation of Cell During Apoptosis
  • 3.4. Fragmentation in the Shear Stress
  • 4. Observation of Membrane Vesiculation on Giant Phospholipid Vesicles
  • 5. Attractive Mediated Interaction Between Membranes is Subject to Bridging Mechanism and Orientational Ordering of Media...
  • 6. Stability of Narrow Necks
  • 7. Suppression of Membrane Vesiculation in Cells
  • 8. Clinical Implications of Membrane Budding Suppression
  • References
  • Index
Chapter Two

Effect of Lipid Bilayer Composition on Membrane Protein Association

Aiswarya B. Pawar*; Xavier Prasanna*,; Durba Sengupta*,,1    * CSIR-National Chemical Laboratory, Pune, Maharashtra, India
┼ Academy of Scientific and Innovative Research, Pune, Maharashtra, India
1 Corresponding author: email address:


Diverse cellular functions are supported by membrane protein assemblies associated with the cell membrane. Although considered to be protein-mediated, membrane components are now being recognized as critical in modulating and sometime dictating function. This chapter discusses the effect of the lipid bilayer, in particular its composition on membrane protein organization. Computational methods have been successful in quantifying transmembrane protein association and general features of dimerization profiles are explored. Understanding the molecular basis of the interactions has lead to the recognition of the lipophobic effects. These nonspecific effects include those that arise from membrane perturbations and lipid chain packing and have been shown to modulate the energetics as well as the structural characteristics of membrane protein dimerization. In addition, specific interactions arising from direct protein-lipid interactions and protein-cholesterol interactions have been suggested to influence membrane protein association. We summarize here a few examples highlighting the role of the lipid bilayer on membrane protein organization.


Protein-lipid Interactions

Membrane protein association

Lipophobic effect

1 Introduction

The cell membrane is the primary barrier for the cell and is involved in the regulation of cellular information networks [1]. In its simplest form, the cell membrane can be considered as a bilayer of lipids exhibiting free lateral diffusion, as suggested by the fluid mosaic model [2]. With advances in experimental techniques, coupled with a better understanding of multicomponent lipid systems, a paradigm shift has been seen in this view of membrane. The cell membrane is no longer considered as a homogenous "sea of lipids" but suggested to exhibit asymmetrical distribution within and across the leaflets [3]. A diverse species of lipids such as saturated and unsaturated phospholipids, glycolipids and sphingolipids as well as cholesterol are present in cell membranes whose composition is dependent on cell type, stress conditions and even cellular age. The complexity in membrane composition is coupled to evidences pointing toward the presence of transient lipid "micro" or perhaps "nanodomains" which differ in composition and physical properties, such as fluidity and thickness [4]. A schematic representation of the cell membrane highlighting these features is shown in Fig. 1. Besides heterogeneity in nature of lipids, the cell membrane hosts a large population of diverse membrane proteins. The most abundant and best-studied membrane proteins which regulate several physiological processes include transmembrane receptors such as receptor tyrosine kinases (RTKs) (represented by the single transmembrane helices in Fig. 1) and G-protein coupled receptors (GPCRs) (corresponding to the multi-transmembrane protein in Fig. 1) [5, 6]. In addition, the cell membrane is intricately associated with the underlying cytoskeletal network [7] (shown by the green (gray mesh below the membrane in the print version) network in Fig. 1). The role of various membrane components in cellular function and how they interact together to function is still not clearly understood.

Figure 1 A schematic representation of the cell membrane depicting the lipid bilayer with various membrane proteins. Phospholipids are depicted with their head groups in orange (gray in the print version) and acyl chains in yellow (light gray in the print version) and glycolipids are shown in deep blue (dark gray in the print version). Cholesterol is shown in cyan with its head group in red (gray in the print version). Single transmembrane proteins of which ErbB2 is a representative member are depicted in magenta (gray in the print version). G-protein coupled receptors (GPCR) are shown as a multi-transmembrane proteins in purple. Peripheral proteins such as the G-proteins are depicted in pink (gray in the print version) and caveolin are depicted in light blue (gray in the print version). The actin cytoskeleton is shown as a green (gray mesh in the print version) lattice beneath the lipid bilayer.

In this chapter, we discuss the interplay between membrane components-proteins, lipids, and cholesterol. The effect of proteins on the surrounding membrane and how in turn the bilayer modulates protein organization has been analyzed using a few interesting examples. We review the contribution of multiscale simulation studies in providing a molecular-level understanding of these processes. Two protein classes, single transmembrane helices that include the ErbB2 family and larger seven transmembrane proteins, GPCRs have been discussed in detail highlighting the membrane effects in protein association. And finally, a simple overview of the energetics of membrane organization is given.

1.1 Role of Membrane Protein Association in Function

Membrane proteins play important roles in several cellular processes and are involved in pathological mechanisms underlying various human diseases [8]. These proteins interact and associate with one another to form large multimers, several of which have physiological roles [9]. In a few cases, association confers function, while in others activity is regulated by their interaction with each other. A classical example involves the growth factor family (ErbB 1-4) belonging to the RTK class of membrane proteins that have been suggested to associate to an active dimer to initiate downstream signaling [10]. These associations are usually transient and the equilibrium between the multimers determines activity. Over expression of ErbB2, presumably leading to increased association have been shown to be oncogenic. Consequently, modulating transmembrane association can modify downstream signaling events and transmembrane peptides targeting ErbB2 have been recently shown to inhibit breast tumor growth and metastasis [11]. Another example of transmembrane association is the GPCR family in which super resolution experimental approaches have confirmed a dynamic equilibrium between various oligomeric species [12, 13]. Although the monomeric species have been shown to be sufficient for function [14], GPCR dimerization has been suggested to have both organizational and regulatory roles [15]. Since GPCRs represent important drug targets [16], the ability of these proteins to exist in several oligomeric states presents a new challenge for targeted drug therapy. An dominant role of lipids in shaping membrane-protein structure [17] and function [18, 19] is emerging, but its contribution to membrane protein organization is still less explored. The need arises to understand membrane protein association and evaluate the factors controlling association.

1.2 Protein Interactions Are Suggested to Be Sequence Dependent

Experimental approaches investigating membrane protein association suggest sequence specificity to be the major factor in driving interaction [20]. Sequence motifs such as the GxxxG motif have been identified as determinants of transmembrane helix association [21] and unique helical interfaces comprising of these residues have been proposed [22]. However, inhibition of protein association due to mutation of key residues "predicted" to be essential for protein-protein interaction, could be reverted back by a second mutation elsewhere along the transmembrane segment [23]. Further, quantitative estimates of transmembrane helix association [24] have revealed key differences from the previous estimates in detergent micelles [21, 25] and via indirect in vivo measurements [26]. Related studies have shown that the lipid bilayer modulates association through sequence-independent effects and membrane composition [27], and fluidity [28] have been suggested to play important roles in helix association.

Similarly for GPCRs, unique dimer interfaces have been proposed from experimental studies [29]. Crystal structure of oligomeric ß1-adrenergic receptor revealed two distinct dimer conformations, suggesting the presence of multiple dimer interfaces [30]. Importantly, membrane composition has also been reported to influence structural organization of transmembrane proteins [31, 32]. It is becoming increasingly clear that "non-protein" contributions are significant in membrane protein organization. Even with current state-of-art technologies [33], experimental approaches are limited in their ability to probe the factors governing membrane protein association. The lack of a "molecular" level insight into the structure and underlying thermodynamics arises due to experimental limitations in structural resolution and lower time-scale sampling.

2 Computational Methods to Analyze...

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