Lung Surfactant Function and Disorder PDF

Preface

There have been major breakthroughs in lung surfactant (LS) research over the last two decades that have changed our concept of how and why the material works well at the lung air–water interface. From the initial ideas of a surface active material lining the alveoli to the seminal concepts of how low surface tension is reached, the classical ideas about Comroe's "extraordinary juice" requires revision and re-thinking. From the early concepts developed by Von Neergard, Pattle, Clements, Avery, and Bangham—to current status and future directions developed by others—LS research has come a long way.

The concept of this volume was developed about two years ago, at a Biophysical meeting and later at the American Thoracic Society meeting where I had the pleasure of meeting a number of upcoming researchers in the field. I was humbled to know how less a biophysicist like myself knew about the clinical and molecular biology aspects of LS. Our physicochemical way of looking at LS as a membranous or colloidal system was difficult to describe to the clinical scientists. This volume is a small contribution in explaining basic and clinical laboratory knowledge to the larger audience and surfactant researchers, at an advanced basic–clinical interface.

Although in recent years there have been a number of excellent reviews on various aspects of LS, like most reviews these tend to encompass a large volume of data and multiple interpretations and do not allow for easily bringing in new concepts from researchers. There are a number of other volumes included in the Lung Biology in Health and Disease series, such as volumes 1, 12, 24, 35, 55, 84, 121, 143 that have chapters devoted to LS related research, and have contributed to our understanding of LS over the last three decades. There is also a single authored volume (vol. 149), that focuses on biophysics as well as clinical aspects of LS at a basic level. There are also a few review books, almost a decade old, written by experts in the field. Normally, review books are written and edited by such experts. However, breaking this norm for this volume was due to my personal situation at the time of conception of this book as a post-doctoral fellow in an obscure university in Canada. At that time I was struggling with the toils and troubles of stable bubbles, and of securing a more permanent position (possibly in another obscure university in Canada). I have enthusiastically pursued respiratory research from my honors student days in India, leading to a masters in Physiology (Biophysics) and Biochemistry, and finally doctoral and postdoctoral training in lung biology. Over the past two decades I have had the opportunity to observe the LS system from a biophysical as well as a clinical viewpoint. During this period what fascinated me about surfactant was that the molecular mechanisms of its action could be interpreted from fields as diverse as neonatal physiology, genetic knockout mice, soft condensed matter, and nanobiology.

I had initially approached some new and upcoming researchers in this field who were at this stage of transition—from postdoctoral to the higher echelons of academia—to either create their own chapter or do so with co-contributors. This volume is thus designed to focus on laboratory research areas of some new and exciting semi-classical concepts of LS that try to encompass biophysics, molecular biology, clinical physiology, developmental and microbiology as well as surface and interfacial chemistry, physics, membranes, soft matter, and molecular imaging. The word "lung" is utilized throughout (and in the title) to replace "pulmonary," considering the presence of LS beyond the alveoli in the upper airways, and its role in asthma and upper respiratory tract disease. Also the parenthesis to the word (dys)function is used since some of the functional aspects of LS are not clear to date, and molecular mechanisms of disease and dysfunction of the material are only emerging.

This book is structured in a format where we attempt to broadly discuss the diversity of molecular composition (Chapters 1–5) and some current methodology in rapid analysis of LS lipids (Chapter 2) in various species and in health and disease (Chapter 1). The current status of surfactant proteins are presented in Chapters 3, 4, and 5. A few surprises have emerged along the way, as we now know that lung surfactant contain different disaturated lipids, other than DPPC (Chapter 1), and that some species breathe fine without this lipid being present in "large" amounts in their surfactant (Chapter 2). Others have recently compressed a fluid phospholipid film to reach near zero surface tensions in captive bubbles (Chapter 6) and observed similar properties of liquid crystalline membranes and LS (Chapter 7). The structure–function property of LS is too vast and detailed, thus I have taken the liberty to select a set of discussions on the function of lipids and lipid–protein systems, from a molecular mechanism and biophysics viewpoint (Chapters 6–13). Some of these (Chapters 9–13) discuss the classical concepts of the "laboratory assigned" roles of the surfactant proteins from SP-A to SP-D, while we wait for SP-Es and Fs to emerge. The book, however, includes other discussions especially for the possible new and emerging role of hydrophobic proteins in processes such as channel activity (Chapters 8 and 14) and in another section as antimicrobials (Chapter 17).

Although the final section of the book deals with (dys)function and disease aspects of surfactant from the clinical (Chapters 16 and 17), physiology (Chapter 15), replacement therapy aspects (Chapter 19), only a few contributions are assembled to provide a sample of such studies (Chapters 15–19). This is due to various aspects of lung disease related to LS discussed in previous books and volumes of this series. Thus I have only chosen a sample few, in order to provide researchers the necessary laboratory experience. I make no naive claims to either comprehend this vast area of respiratory distress, nor have I tried to attempt to provide a comprehensive and all inclusive glimpse at the complexity of LS dysfunction. My sincerest apologies to numerous upcoming and excellent researchers in this area for not being able include their work, due to shortage of textual space. This will possibly also allow one to avoid extreme physical discomfort and consumption of muscle (brain) relaxants which may be required while handling this volume. A future volume in editorial collaborations with experts in the clinical areas may be forthcoming, depending on the reception of this volume by the LS community.

I must confess my personal heavy-handedness in dealing with the Biophysics section (Chapters 6–14) since this is one area I feel comfortable with compared to my naivety in most others. (After all how do we study a floating membrane in the lung?) This section deals with the concept of low surface tension in the lung that may be induced by a fluid lipid defying some classical concepts (Chapter 7), to applying cell membrane "lipid rafts" or structural concept to surfactant (Chapter 6). Such methods rely heavily on new and powerful physicochemical techniques utilized to pin down single molecules, molecular motions, and aggressively define LS as soft matter—either inside an atomic force microscope (Chapters 11 and 12) or a computer (Chapter 9). Some of this methodology also requires a certain level of mathematical sophistication to be defined by experts (some of these colleagues are clinical scientists with doctorates in physical chemistry and physics). Someday these technologies may be helpful to new and emerging researchers who venture into the intricate world of nuclear spins of surfactant proteins (Chapter 11), knock-out genes (Chapter 13), and to smash DPPC under ion-beams (Chapter 10).

It would be a fallacy in even trying to acknowledge all the colleagues, co-authors, and experts that I have met and discussed LS research with for over two decades, having thus directly/indirectly contributed to this volume. However, I wish to thank a few, such as Dr. Claude Lenfant (Executive Editor of this series) for inviting me to edit this book, Prof. Fereidoon Shahidi (Biochemistry, Memorial University), and Anita Lekhwani (Acquisitions Editor, Taylor & Francis Group), for help in providing the necessary enthusiasm, editorial, and publication guidelines, without which this volume would never have seen publication. I would be remiss not to acknowledge the help and support of my mentor Dr. Kevin Keough (President, Alberta Heritage Foundation for Medical Research, Canada), who has continuously and enthusiastically encouraged as well as criticized my continuous adventure into the world of LS and membranes. A belated gratitude goes to the late Prof. Haripada Chattopadhayay of Presidency College, Kolkata (West Bengal, India) who had first showed me how breathing patterns of humans change due to circadian rhythms, in a dark room in India. Incidentally this room was above a floor of the Physics department, where C.V. Raman and S. Bose extrapolated their ideas on molecular vibration patterns and Bose– Einstein condensates, more than half a century ago. Funding for my studies in North America is gratefully acknowledged from the Medical Research Council of Canada, Ontario Thoracic Society, Canadian Lung Association, National Scientific and Educational Research Council, and recently from Canadian Institute of Health Research, Canada Foundation for Innovation, and Memorial University of Newfoundland.

Having actually watched the whales spray their lung surfactant in the bays of Newfoundland, to seeing and touching the terminal methyl chains of DPPC— or observing neonatal recovery after LS administration—I feel there are many fascinating discoveries yet to be made on Comroe's "extraordinary juice." As the master of analogy Pierre De Gennes stated in his Nobel Lecture "it is perhaps amusing to note that there is some overlap in thought between people who study high brow string theories and description of soaps" (see Chapter 6 for details). I sincerely hope this volume provides such overlap in lung surfactant researchers from biology, chemistry, physics, computer science, and medicine.