Membranes

Raz Jelinek

• Publisher: De Gruyter
• Year: 2018
• ISBN:
  9783110453904
• Edition: 1
• Topic: Technology & Engineering
• Subtopic: Materials Science
• Index: Technology & Engineering

Describes the properties of cellular membranes and their relationship with fundamental biological processes. This book provides insight on the chemistry, structures, model systems, and techniques employed for studying membrane properties and processes. A major focus is on the prominence of membranes in diverse physiological processes and disease, as well as applications of membranes and biomimetic membrane systems in varied disciplines. The book aims to illuminate the significance and beauty of membrane science, and serve both as an entry point for scholars wishing to embark on membrane research, as well as scientists already working in the field.

1Introduction

Arguably, the membrane has a good claim of being the most universal cell component as it is found in all cells and in most intracellular organelles and compartments. While different cellular membranes have distinct functionalities, some underlying properties of membranes can be considered as generic in nature; by maintaining a physical separation between the “in” and “out” of a cell or an intracellular organelle, membranes both compartmentalize cell contents and functionalities, and shield the molecular “soup” inside cells and organelles from their external environments. Membranes, however, are also semi-permeable and need to regulate transport of materials into and out of the cell (or cell compartments), a critical function that is generally carried out with the aid of specialized proteins embedded in the membrane matrix. Membranes exhibit other prominent roles in cellular physiology, including maintenance of cell shapes, serving as docking sites for extra- and intracellular biomolecules, and comprising physical junctions for regulatory processes.

While processes occurring at the plasma membrane (which encloses the entire cell) have attracted the widest research efforts, other membranes feature prominently inside the cell, including the nuclear membrane and the mitochondrial membrane, each exhibiting distinctive functions that are intimately linked to their compositions and macroscale organizations. The plasma membrane itself exhibits significant structural diversity – differences in membrane properties are apparent between microorganisms, between cell types, and also within the same cells depending upon the occurrence of biochemical processes or disease conditions. These features have made membranes the focus of intense interdisciplinary research, integrating chemistry, biology, physics, pharmaceutics, and related scientific disciplines.

Figure 1.1 depicts a typical architecture of the plasma membrane. The large majority of membranes consist of lipid bilayers as the molecular scaffolding. The bilayer blocks passage of water molecules and prevents water-dissolved substances at each side from mixing. Figure 1.1 also highlights the incorporation within the bilayer of membrane-associated peptides and proteins which play critical roles in regulation of cell processes, communication, metabolism, and other processes. As shown in Figure 1.1, the bilayer-spanning segments of membrane proteins adopt distinct structures, usually helical conformations or beta-sheets. Channels through which molecules can traverse the lipid bilayer are among the functionally critical organizations of membrane proteins. In many cell types, the bilayer also engages in interactions with the cytoskeleton – the filament network tasked with maintaining overall cell morphology and shape. Such interactions usually occur through specific domains of membrane-associated proteins which tuck in the cytoskeleton compartment, thus linking it to the cell membrane.

The cartoon in Figure 1.1 shows different components of the plasma membrane and associated constituents. The lipid bilayer scaffold (green) hosts membrane proteins (yellow and orange) displaying bilayer-spanning domains as well as segments protruding into the extracellular space and cytoplasm, respectively. The cytoplasmic domains of certain membrane-associated proteins also anchor the cytoskeleton network (black).

Figure 1.1: Architecture of the plasma membrane. Reprinted from Chemistry and Physics of Lipids, vol. 163, Pabst G. et al., Applications of neutron and X-ray scattering to the study of biologically relevant model membranes, Pages No. 460–479, Copyright (2010), with permission from Elsevier.

This textbook aims to provide a broad overview of modern membrane science. In light of the wide scope of the field, choices had to be made concerning foci and breadth of discussions. Accordingly, membranes of animal cells are mainly discussed, primarily human cells, while prokaryotes and archaea are covered to a lesser extent. The components of cellular membranes, their organizations, and features of membrane processes are the core topics of the book. Membrane proteins are discussed in a more cursory manner as these important biomolecules deserve their own “textbook”; indeed, the reader is referred to the many excellent treatises devoted to membrane proteins.

Thematically, chapters in this textbook are structured according to the diverse facets of membrane studies. The main molecular constituents of cellular membranes, their organizations, and the properties of distinct membrane domains and compartments are discussed in Chapter 2. Subsequent chapters focus on membranes of intracellular organelles (Chapter 3), characteristics of membranes in cells belonging to different organisms and life domains (Chapter 4), and physiological membrane-like protective layers in the human body (Chapter 5). Chapter 6 summarizes the diverse model systems and experimental techniques applied in membrane investigations. Indeed, many of those strategies aim to surmount the formidable complexity of actual cellular membranes, a considerable hurdle encountered by scientists aiming to decipher the inner workings of the membrane. Chapter 7 presents a comprehensive overview of membrane processes, underscoring the centrality of the membrane in cell physiology. The prominence of membranes, membrane targeting, and biomimetic membranes in disease and biomedicine is discussed in Chapter 8. Finally, examples of materials and technologies inspired by the cell membrane are presented (Chapter 9). Certain overlap naturally exists among various subjects, and accordingly some topics are discussed in more than one chapter.

This textbook is designed to introduce the reader to membranes, emphasizing current research activities and directions. While my aim is to illuminate the wider contours of the field, many of the topics are presented and discussed in the context of specific examples from published studies. Naturally, considering the huge body of work on cellular membranes, only a small fraction of representative studies have been included and the reader is encouraged to further explore the numerous publications related to membranes – textbooks, review articles, and scientific reports. Principally, this book is not intended just for experts working in membrane sciences, but rather to a broader scientific readership. Yet, knowledge of basic biological and chemical concepts is a prerequisite for grasping many of the concepts and examples presented.

It should also be emphasized that while our knowledge and understanding of membranes and membrane processes are extensive, there are still unknowns and “enigmas” yet to be deciphered. Indeed, new membrane-associated biomolecules and processes are still being discovered, shedding light both on normal cell physiology and on disease. Overall, this textbook should serve as a useful “entry point” to the vast universe of membranes, their properties, and functions. My hope is that the book will expose the reader to the beauty, impact, and also complexity of cellular membranes. I am certain that the study of membranes will continue to expand and evolve, providing better understanding of fundamental biological processes, opening the way to new therapeutic avenues, and perhaps even illuminating the secrets of life.

2Membrane structure and composition

Chemically speaking, membranes are defined as “supramolecular assemblies,” i.e. molecular entities whose properties are determined both by the individual building blocks and by their micro- and macroscale organizations, mutual interactions, and synergistic effects. Indeed, the molecular constituents of membranes have critical roles in shaping and modulating their cooperative properties. The “mosaic model” (Figure 2.1) has been an early, simplistic albeit powerful model for membrane architecture and molecular organization. According to this signature model, outlined by Singer and Nicolson in the early 1970s, membranes are composed of an assortment of molecules and domains that together form an intricate “mosaic” shaping the plethora of structural and functional properties of the membrane. The mosaic model accounts for both the rapid lateral mobility of lipids and proteins within each of the two sheaths in the membrane bilayer and the slow migration between the two bilayer sheaths (“flip-flops”). The model also aimed to explain functional observations, suggesting that the lipids mainly serve as a host matrix for proteins which exert biological activity. The mosaic model also stipulates that the different molecules in the membrane – lipids, lipid derivatives, proteins, sugars, and their conjugates – maintain complex dynamic equilibria. Indeed, diverse biological processes associated with the membrane arise from interactions among embedded molecules and concomitant changes in membrane properties.

This chapter focuses on the molecules comprising membrane scaffolds, particularly lipids – the basic building blocks of the bilayer scaffold. Different types of lipids and lipid derivatives are discussed herein, and their contributions to membrane properties are assessed. The second part of this chapter describes distinct units, domains, and compartments formed through co-assembly of several lipid species, particularly the important and initially controversial lipid rafts. Finally, we will touch on the huge field of membrane-associated proteins, arguably the most important functional units in cellular membranes.

It is important to note that the discussion in this chapter does not cover other important coating layers in microorganisms, such as the peptidoglycan-based outer cell wall in Gram-negative bacteria or the glycocalyx – the protein–polysaccharide conjugate matrix encasing several cell species. Indeed, as emphasized in the text, a fundamental feature of the cell membrane, which distinguishes it from other biological barriers such as the peptidoglycan and glycocalyx, is its fluidity – the mobility of the molecular constituents which bestows the membrane with many of its important structural and functional properties.

2.1Lipid phases

Lipids are the fundamental building blocks of membrane scaffolds. As a general definition, lipids are hydrophobic, and most lipid molecules are also amphiphilic (containing both polar and non-polar domains). Hydrophobicity and amphiphilicity are central in affecting self-assembly of lipids in water, promoting the formation of distinct “compartments” – the essence of biological membranes. More than a thousand lipid molecules have been identified in cellular membranes in the human body; countless more take part in cell processes which are not necessarily or exclusively associated with a membrane.

Figure 2.1: The “mosaic model” of cellular membranes. Proteins and other membrane-embedded molecules are floating within the lipid bilayer framework.

Polar lipids are the primary molecular constituents of the cellular membrane. These lipids generally comprise a polar or c...