Table Of ContentCell Membranes
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Cell Membranes
Lukas K. Buehler
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Cell Membranes
Lukas K. Buehler
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ISBN 978-0-8153-4196-3
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Buehler, Lukas K.
Cell membranes / Lukas Buehler.
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ISBN 978-0-8153-4196-3
1. Cell membranes. 2. Membranes (Biology) I. Title.
QH601.B84 2015
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I dedicate this book to the memory of Hansgeorg Schindler (1943–2001) who died
climbing the Austrian Alps. He was my first mentor and master thesis advisor from
whom I learned not only the rigor of scientific research, but also the passion for
one’s work. A physicist by training, he dedicated his life to the study of ion chan-
nels, both in model membrane systems and, in later studies, by single-molecule
dynamics in order to make the complex structure of cell membranes amenable to
quantitative analysis.
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Cell Membranes
Lukas K. Buehler
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Preface
Why write a book on cell membranes? Being a full-time teacher now, writing
this book on cell membranes brings together two loves—studying ion channels
as a graduate and a postdoctoral student and, more recently, teaching biology to
undergraduate students. Writing this book caps a scientific career in research into
the structure–function relationship of ion channels using mostly model membrane
systems. I first fell in love with cell membranes as a student at the University of
Basel, Switzerland, when a graduate student in Hansgeorg Schindler’s biophysics
course demonstrated the reconstitution of single channels in planar lipid bilay-
ers. The simplicity and beauty of the ensuing single-molecule activity—repeatedly
sweeping across the green screen of an oscilloscope— elicited solely from recon-
stituted synthetic phospholipids and a small amount of gramicidin peptide solu-
tion, introduced me to a core truth about cell membranes as a complex system:
their function is the result of lipids and proteins working together to produce an
effect that neither could do on its own.
When I started writing the book around 2003, the existing fluid-mosaic model
of cell membranes as conceived by Nichols and Singer in 1971 was ripe for revi-
sion in order to better account for the existence of lipid domains. The accelerating
pace of determining high-resolution structures of membrane proteins enhanced
the insight into the complex behavior of cell membranes. Particularly, progress
in solving the atomic structures of channels has dramatically changed the field’s
rudimentary understanding of transport mechanisms. In the 1970s, kinetic mod-
els with multiple energy barriers along cylindrical pore models tried to explain ion
selectivity and specificity of transport, but were sorely lacking structural evidence.
Today, molecular modeling based on detailed high-resolution structures of trans-
porters in various states of activity shows the sophisticated gating and selectivity
mechanisms of proteins, which undergo conformational changes to capture sub-
strates on one side of the membrane and release them on the opposite side.
Cell membranes are essential components of all living organisms—bacteria, ani-
mals, and plants. Membranes regulate nutrient uptake and waste removal, protect
against environmental toxins and infectious microorganisms, store energy like
batteries, catalyze chemical reactions, recognize stimuli from their surroundings,
and transduce signals from external hormones and growth factors into intracel-
lular responses. Two of the most fundamental biological processes—respiration
and photosynthesis—are carried out by membrane-bound enzymes. Membranes
being such centrally important structures of cells, it is thus not surprising that, on
the one hand, teaching about membranes becomes an indispensable component
of any course in the life sciences, from biophysics to neurobiology, from cell biol-
ogy to physiology, from microbiology to medicine. On the other hand, learning
about cell membranes expects from students an understanding of all the natural
sciences, and a grasp of chemistry and physics, of mathematical modeling, and
of engineering. With this textbook, faculty can use an interdisciplinary approach
when preparing a lecture on cell membranes. A cell biologist can find information
about the biophysical properties of membrane lipids and bilayer organization,
and a structural biologist will find information about physiology and hormone
receptors.
This book therefore offers a long-overdue synthesis of our knowledge of cell
membranes. I organized the book to guide the reader first through basic descrip-
tions and explanations of the molecular composition and physical properties of
cell membranes, surveying the structural diversity of membrane proteins and
lipids separately. The book then moves on to discuss how the functions of both
membrane proteins and lipids depend on each other to promote the four basic
functions of cell membranes: being barriers, mediating exchange of molecules
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viii PREFACE
and information to maintain cellular compartments, promoting signaling and
adhesion, and being metabolically self-renewing cellular structures. Having
always had an interest in the evolutionary history of life, I have included in the
book a special emphasis on the biological diversity, evolution, and origins of
membranes. Core questions in modern biology are in the understanding of the
complex interactions of many molecular components to produce an orderly
cellular process and how membranes contribute to information processing in
living organisms. To this end, the book describes the use of model membrane
systems to gain insights into membranes in living cells. With this reductionist
approach, biologists are able to answer important questions about the struc-
tural organization of cells, and how this molecular organization contributes to
the behavior of organisms.
The reader will also come across, and hopefully appreciate, the use of categories
for proteins and lipids and the need to choose from alternative ways to catego-
rize proteins and lipids by structure, function, secondary structure composition,
membrane location, or membership in families and superfamilies. I hope that the
corresponding tables are useful and function as an easy reference for the reader.
Many more tables could have been generated, given the large numbers of known
proteins and lipids, and relying mostly on examples was often the best option
in order to stay on message and not overwhelm the topic with too many details.
Occasionally, I perceived a real need to abandon or tweak existing categories, and
one of the novel categories I use in this book employs the term ‘surface-bound’
membrane protein—that is, to combine peripheral, lipid-anchored, and mono-
topic membrane proteins into one group distinct from transmembrane proteins.
Conventional terms like integral and intrinsic, while still valuable for methodo-
logical discussions, fall short of describing the variation in the ways membrane
proteins are associated with lipid bilayers. Interestingly, reviewers sensed my
occasional struggle and the work that went into making sense of existing but
conflicting categories and nomenclature. A good example is the use of the terms
phospholipids and glycolipids, both of which are ambiguous, yet have clear mean-
ing to the veteran scientist, until they do not. Thus, I hope the ‘veteran’ reader
will appreciate my approach of consolidating terminology and making choices in
favor of some but not other terms.
There is yet another approach that I felt was necessary: an emphasis on concepts
rather than methods, although each chapter ends with a list of reading materi-
als where experimental information can be found about the topics covered. As
a result, the appendices in the book include information, albeit concise, about
amino acid properties important for protein structure prediction methods, the
diversity and properties of detergents, and reconstitution strategies to solve high-
resolution structures through X-ray crystallography, nuclear magnetic resonance
(NMR), and electron diffraction techniques. Many other experimental methods in
the biochemical, structural, and genetic analysis of membrane lipids and proteins
are mentioned (and some are explained in more detail) throughout the chapters.
I want to thank many people who have helped me become the scientist and teacher
I am today: Hansgeorg Schindler and Jurg P. Rosenbusch at the Biozentrum of
the University of Basel, where I learned the ropes of membrane biochemistry and
ion channel reconstitution and functional analysis; Richard Zimmermann and
Matthias Falk who showed me the amazing world of in vitro synthesis of mem-
brane proteins; and Maurice M. Montal and Reza Ghadiri who introduced me
to the world of synthetic, channel-forming peptides. While always working with
synthetic bilayers, these scientists all came from different backgrounds, allowing
me to see and think like a physicist, a cell biologist, a chemist, or a neurobiol-
ogist. I worked with bacterial porins and mammalian gap-junction channels, with
synthetic peptides mimicking the nicotinic acetylcholine receptor pore struc-
ture, and cyclic nanotubes, a non-natural peptide designed to mimic the channel
architecture of gramicidin peptides. Thus, at the very end of my research career, I
came full circle to my very first look at a cell membrane.
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PREFACE ix
Acknowledgments
The author and publisher of Cell Membranes gratefully acknowledge the contribu-
tions of the following reviewers in the development of this book:
Nathan N. Alder, University of Connecticut; Anthony Baines, University of Kent;
Siddhartha Das, University of Texas at El Paso; Robert Ernst, Goethe University
Frankfurt; Said Eshaghi, Scripps Research Institute; Matthias M. Falk, Lehigh
University; Aileen F. Knowles, San Diego State University; M.K. Mathew, National
Centre for Biological Sciences in Bangalore, India; Douglas D. McAbee, California
State University Long Beach; Suchetana Mukhopadhyay, Indiana University;
Mary F. Roberts, Boston College; John Voss, University of California at Davis; Paul
Young, University College Cork.
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