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About this book

This book compiles the fundamentals, applications and viable product strategies of biomimetic lipid membranes into a single, comprehensive source. It broadens its perspective to interdisciplinary realms incorporating medicine, biology, physics, chemistry, materials science, as well as engineering and pharmacy at large. The book guides readers from membrane structure and models to biophysical chemistry and functionalization of membrane surfaces. It then takes the reader through a myriad of surface-sensitive techniques before delving into cutting-edge applications that could help inspire new research directions. With more than half the world's drugs and various toxins targeting these crucial structures, the book addresses a topic of major importance in the field of medicine, particularly biosensor design, diagnostic tool development, vaccine formulation, micro/nano-array systems, and drug screening/development.
Provides fundamental knowledge on biomimetic lipid membranes;Addresses some of biomimetic membrane types, preparation methods, properties and characterization techniques;Explains state-of-art technological developments that incorporate microfluidic systems, array technologies, lab-on-a-chip-tools, biosensing, and bioprinting techniques;Describes the integration of biomimetic membranes with current top-notch tools and platforms;Examines applications in medicine, pharmaceutical industry, and environmental monitoring.

Table of Contents


Structural and Mechanical Characterization of Supported Model Membranes by AFM

Several cellular processes, including adhesion, signaling and transcription, endocytosis, and membrane resealing, among others, involve conformational changes such as bending, vesiculation, and tubulation. These mechanisms generally involve membrane separation from the cytoskeleton as well as strong bending, for which the membrane chemical composition and physicochemical properties, often highly localized and dynamic, are key players. The mechanical role of the lipid membrane in force triggered (or sensing) mechanisms in cells is important, and understanding the lipid bilayers’ physical and mechanical properties is essential to comprehend their contribution to the overall membrane. Atomic force microscopy (AFM)-based experimental approaches have been to date very valuable to deepen into these aspects. As a stand-alone, high-resolution imaging technique and force transducer with the possibility to operate in aqueous environment, it defies most other surface instrumentation in ease of use, sensitivity and versatility. In this chapter, we introduce the different AFM-based methods to assess topological and nanomechanical information on model membranes, specifically to supported lipid bilayers (SLBs), including several examples ranging from pure phospholipid homogeneous bilayers to multicomponent and phase-separated SLBs, increasing the bilayer complexity, in the direction of mimicking biological membranes.
Berta Gumí-Audenis, Marina I. Giannotti

To Image the Orientation and Spatial Distribution of Reconstituted Na+,K+-ATPase in Model Lipid Membranes

Imaging of sub-optical dynamic features, such as functional membrane nanodomains that are short-lived and proteins that are embedded in such nanodomains, is a challenge with the currently available imaging techniques because such features of interests are very dynamic. Our approach to image dynamic suboptical features is based on a GUV-collapse method followed by high-resolution imaging. We have functionally reconstituted Na+,K+-ATPase, a P-type transmembrane ATPase protein, into free-standing giant unilamellar vesicles (GUVs) which are collapsed to form planar lipid bilayer (PLB) patches within the ∼10 ms time scale. Using our method, we have successfully imaged the PLB patches using atomic force microscopy under physiological conditions to quantify orientation and density of Na+,K+-ATPase in membrane with nanoscopic domains.
Tripta Bhatia, Flemming Cornelius

Asymmetric Model Membranes: Frontiers and Challenges

Cellular membranes are highly complex liquid-crystalline entities, which makes it difficult for researchers to connect specific components and their effects on overall membrane structure, function, and biochemical and biophysical properties. To circumvent this issue, model membranes with controlled compositions have since become a staple of biomembrane research, helping researchers better understand the inner mechanisms of cell membranes. These simplified lipid systems have predominately been composed of symmetric lipid bilayers – where both leaflets are composed of the same constituents. Only recently has there been a shift toward the use of bilayer systems with asymmetric distributions of lipids across the two monolayers. This is because most (if not all) biological membranes possess lipid asymmetry which has sparked an intense desire to study its effects on membrane structure, dynamics, and membrane-associated molecules. In recent years, many have sought out to develop asymmetric model construction methods to facilitate these studies. In this chapter, we aim to describe novel and relevant asymmetric preparation methods, as well as their pros and cons to paint an image of the current state of biomembrane research and the challenges the field faces. Ultimately, these techniques are at the forefront of an exciting biomembrane renaissance.
Michael H. L. Nguyen, Brett W. Rickeard, Mitchell DiPasquale, Drew Marquardt

Modeling of Cell Membrane Systems

The mechanisms that take place in or through cell membranes are vitally important for all living organisms. The molecules embedded in or associated to membranes, such as transmembrane proteins, behave dynamically to perform their functions. Although experimental techniques have improved considerably in recent decades, when combined with computational means of modeling, they reveal secrets behind the mechanisms related to membrane systems. The resolution of the structures of membrane proteins has become trivial recently using computerized prediction tools. The worldwide accumulation of structural data in databases enables the application of in-silico methodologies. Simulations, together with the various lipid membrane models, provide information through the dynamic exploration of conformational space. In this chapter, the basics of modeling are discussed, with a focus on molecular dynamic modeling methodology. In addition to modeling, visualization and analysis tools are also mentioned.
Tuğba Arzu Özal İldeniz

Molecular Dynamics Studies of Nanoparticle Transport Through Model Lipid Membranes

Transport of materials through cell membranes is of significant interest. We consider specifically the transport of gold nanoparticles that are in current use for delivery of pharmaceuticals, photothermal therapy, as contrast agents for imaging, and for targeted cancer therapy. We use coarse-grained molecular dynamics simulations to “observe” details of interactions between nanoparticles and a lipid bilayer model membrane during the permeation process. The nanoparticles are characterized at the molecular level (distributions of ligand configurations, their dependence on ligand length and surface coverage). Observation of membrane properties that agree with experimental values validates the simulations. We investigate the mechanisms of permeation of a gold nanoparticle, with either hydrophobic (alkane-thiols) or hydrophilic (PEG (polyethyleneglycol)) ligands attached via a sulfur covalent linkage to spherical (or nanorod) gold cores, and their dependence on surface coverage, ligand length, core diameter, and core shape. Lipid response such as lipid flip-flops, lipid extraction, changes in order parameter of the lipid tails are examined in detail. The mechanism of permeation of a PEGylated nanorod is shown to occur by tilting, lying down, rotating, and straightening up. Information provided by molecular dynamics simulations helps to understand why some systems work better than others, and aids design of new ones.
Cynthia J. Jameson, Priyanka Oroskar, Bo Song, Huajun Yuan, Sohail Murad

Investigation of Cell Interactions on Biomimetic Lipid Membranes

Cell membrane is one of the most exciting biointerfaces by which the cell, the smallest living unit, orchestrates its communication/interaction with its surrounding, vital for its survival. Design of suitable model systems with similar functionalities could prove themselves as useful platforms to focus on membrane-mediated cellular processes such as cell–cell and cell–surface interactions. Biomimetic lipid membranes are able to sustain the structure and fluidity of the cell membrane, and could mimic its dynamic complexity. In this chapter, an overview of cell interactions on biomimetic lipid membranes is given with a focus on supported lipid bilayers.
Abdulhalim Kılıç, Fatma Neşe Kök

Tethered Lipid Membranes as Platforms for Biophysical Studies and Advanced Biosensors

The cellular membrane is a highly complex and sophisticated biological architecture that hosts a vast repertoire of biological machinery. This machinery is essential for many vital processes, from nutrient import to cell-cell communication and sensory detection including touch, taste, smell, vision and auditory signals. Therefore, the cellular membrane hosts a vast number of receptors that are highly specific for signaling molecules, hormones and receptors that detect various elements in the cellular surrounding that affect the functioning of the cell [1].
Jakob Andersson, Wolfgang Knoll

Biomedical Applications: Liposomes and Supported Lipid Bilayers for Diagnostics, Theranostics, Imaging, Vaccine Formulation, and Tissue Engineering

Liposomes and supported lipid bilayers (SLBs) are having an increasing impact in designing new biomedical approaches owing to their cell-like structures and native biophysical environment. In particular, as membrane proteins are target of 60–70% of pharmaceutical drugs in the research and industry, liposomes and SLBs denote unique and versatile capabilities in membrane protein research compared to the conventional systems, which have significant challenges in handling membrane proteins without denaturation and loss of function. Besides, the integrations of liposomes and SLBs into micro- and nano-array format open new avenues to create biochip strategies for modern clinical use. In this chapter, we extensively review biomedical applications of liposomes and SLBs through (i) sensing strategy for diagnostics and (ii) theranostics and labelling capability for imaging, (iii) carrier roles for vaccines, and (iv) tissue engineering approaches for multiple cellular processes. Integrated strategies such as lithography and array formation will be also discussed here in order to envision the potential applications of liposomes and SLBs in the near future.
M. Özgen Öztürk Öncel, Bora Garipcan, Fatih Inci

Lipid Bilayers and Liposomes on Microfluidics Realm: Techniques and Applications

Liposomes and lipid bilayer systems are one of the most ubiquitous structures in the living world, with complex structural features and a variety of biological functions in a constrained milieu. Redesigning and reprogramming these structures as biomimicking components will enable us to investigate basic biophysical and pharmacological processes within intra- and extracellular environments. Microfluidics, an enabling and disruptive technology, have greatly attracted this field by presenting unique capabilities, such as reduction in fluidic volumes, automation, and high-throughput, which have not been introduced with other technologies. In this chapter, a broad perspective and a variety of applications of microfluidic-associated methods were reviewed comprehensively.
Fatih Inci

Biomimetic Model Membranes as Drug Screening Platform

Biomimetic model membranes were inspired by natural cell membrane and are rapidly progressing in the field for varied applications, especially for drug screening studies. Biomimetic lipid membranes such as lipid monolayer, lipid vesicles, and supported lipid membranes have been constructed to investigate the cell membrane and membrane protein interaction with various drugs. Also, biomimetic lipid membranes provide an experimental platform to understand disease at the molecular level, which is also an important step for developing new therapeutic agents. This chapter covers biomimetic model membrane types utilized to screen drug–membrane and drug–receptor interactions, characterization techniques, and an overview of recent work in the field.
Rumeysa Bilginer, Ahu Arslan Yildiz

Biomimetic Membranes as an Emerging Water Filtration Technology

Biomimetic membranes have high water permeability with high selectivity. Recent developments will increase their applications and variety in membrane technologies. This chapter focuses on the type and characteristics of water channels that can be used in these membranes. Also, strategies that can be used for fabrication of biomimetic membranes; lipid/polymer types and concentration that can be used in these membranes; and substrate types that are appropriate to use are summarized in details. The chapter is continued with applications of biomimetic membranes for the treatment of water and wastewater.
Reyhan Sengur-Tasdemir, Havva Esra Tutuncu, Nevin Gul-Karaguler, Esra Ates-Genceli, Ismail Koyuncu

Applications of Lipid Membranes-based Biosensors for the Rapid Detection of Food Toxicants and Environmental Pollutants

The exploitation of lipid membranes in biosensors has provided the ability to reconstitute a considerable part of their functionality to detect trace of food toxicants and environmental pollutants. Nanotechnology enabled sensor miniaturization and extended the range of biological moieties that could be immobilized within a lipid bilayer device. This chapter reviews recent progress in biosensor technologies suitable for environmental applications and food quality monitoring. Numerous biosensing applications are presented, putting emphasis on novel systems, new sensing techniques, and nanotechnology-based transduction schemes. The range of analytes that can be currently detected include phenols, insecticides, pesticides, herbicides, heavy metals, toxins, allergens, antibiotics, microorganisms, hormones, dioxins, genetically modified foods, etc. Technology limitations and future prospects are discussed, focused on the commercialization capabilities of the proposed sensors.
Georgia-Paraskevi Nikoleli, Dimitrios P. Nikolelis, Christina G. Siontorou, Marianna-Thalia Nikolelis, Stephanos Karapetis


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