Keratin and Keratinization; an Essay in Molecular Biology
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INTERNATIONAL SERIES OF MONOGRAPHS ON PURE AND APPLIED BIOLOGY Division: MODERN TRENDS IN PHYSIOLOGICAL SCIENCES General Editors : P. Alexander and Z. M. Bacq Volume 12 KERATIN AND KERATINIZATION OTHER TITLES IN THE SERIES ON PURE AND APPLIED BIOLOGY Vol. KERATIN AND KERATINIZATION An Essay in Molecular Biology E. H. Mercer, D.Sc, Ph.D. Chester Beatty Research Institute: Institute of Cancer Research, Royal Cancer Hospital, London PERGAMON PRESS NEW YORK • OXFORD • LONDON • PARIS 1961 PERGAMON PRESS INC. 122 East 55th Street, New York, 22, N. Y. 1404 Neiv York Avenue N.W., Washington 5 D.C. PERGAMON PRESS LTD. Headington Hill Hall, Oxford 4 & 5 Fitzroy Square, London, W.l PERGAMON PRESS S.A.R.L. 24 Rue des Ecoles, Paris, V. PERGAMON PRESS G.m.b.H. Kaiserstrasse 75, Frankfurt am Main Copyright © 1961 PERGAMON PRESS LTD. Library of Congress Card No. 60-53516 Set in Imprint 11 on 12 pt. and printed in Great Britain by BELL AND BAIN LTD., GLASGOW, SCOTLAND This book is dedicated to the memory of W. T. ASTBURY Contents Preface XI Acknowledgements xiii I Keratin and Molecular Biology 1 Macromolecules and biology 1 Orders of magnitude 3 Types of fibrous proteins and their classification 5 Birefringence 10 X-ray methods 11 14 The a, j8 and collagen patterns Stabilization 19 Ecdysis 22 Distribution of the fundamental fibre-types 22 Some difficulties in defining a keratin 27 The significance of the variable amino acid composition 31 The fine structure of cells 34 Electron microscopy and cytology 34 The cell surface, its specializations and intercellular adhesion 37 The cell membrane 37 Cilia, flagella, etc 39 Surface invaginations 40 Specializations of opposed surfaces. Cell contacts 40 Desmosomes 41 Interdigitation of confronted membranes 43 The differentiation of surface organelles 44 Cytoplasmic structures 45 Particulates 45 Membrane systems 46 The nucleus 48 Differentia 48 The phylogeny of keratinization 49 II The Keratinized Tissues 53 Generalized histology of the vertebrate epidermis 53 Dermis and epidermis 53 55 The epidermis . The epidecmalH^H^mUyfamily of cells 57 LIBRARY «^> V MASS.mat: / Q*^ 81317 <* CONTENTS The differentiation of epidermal cells Hard and soft keratins The specialized appendages Localized epidermal thickenings Scales Horns The digital tips : claws, nails, hoofs Feathers Hairs The phylogeny of hair Other possibly keratinized structures III Differentiation and Protein Synthesis The cytology of keratinizing cells The basal layer cells Cell contacts during differentiation The dermoepidermal junction The development of basal membranes and their role in the formation of epithelia The differentiated layers and the variety of cell products The epidermis Tonofibrils . Keratohyalin The hair follicle Intracellular differentiation in the hair bulb The feather follicle The avian secreted keratins The synthesis of protein in epidermal systems Cytology of cells which form protein Biochemistry of protein synthesis Secondary and tertiary structures Synthesis in retaining systems Synthesis in fibre-forming systems The supermolecular organization of fibrous tissues (tertiary structure) Macromolecular fibrous texture Fibrogenesis Collagen Fibrous insulin Silk fibroin—aggregation of the molecule after unfolding Organization of fibrous tissues Epidermal fibrils IV The Growth of Epidermal Structures The epidermis as a growing organ CONTENTS Mitosis in the basal layer 135 General theories of growth 138 Periodic growth and cyclic activity 143 Control of epidermal growth 146 Competition 149 Patterns of hair growth and control 150 Zig-zags, curls and crimps 156 Allometric growth 159 Molecular and Macromolecular Structure 161 The present status of the chemical structure of the keratins 161 End groups 161 Molecular structure 163 Methods of partial degradation 163 Non- destructive methods X-ray diffraction 164 The low-angle pattern 165 The wide-angle pattern 170 The elastic properties and the structure of hair 172 Current crystallographic analysis 176 Pleated sheet configurations—Silk fibroin . 179 Helical configurations—The a-helix . 181 Coiled coils and a-filaments 183 The organization of a-filaments into larger structures 187 The a-j8 transformation in terms of the a-helix 188 The non-crystalline fraction 190 Other methods of determining chain configuration 194 Optical rotation and rotary dispersion 194 Infra-red spectra and structure 196 Deuterium exchange 200 The cross-/? pattern 200 Other a-proteins 202 Some a- and jS-proteins of insect origin 203 Feather keratin 205 VI The Keratinization Process 210 The hard keratins 210 The development of orientation 211 The development of stability 214 Thiol and disulphide groups during keratinization 217 Nucleic acids and synthesis 219 Metabolic enzymes 221 Glycogen 221 Acid mucopolysaccharides and Schiff-reactive substances 221 Phosphatases 222 CONTENTS Lipids Water content The fine histology of the hair follicle in the keratinization zone The cortex The cuticle The inner root sheath Soft keratinization The epidermis Keratinization of horn Follicular nutrition and the entrance of sulphur Soluble products of partial keratinization Extracts from the pre-keratinized zone Soluble derivatives of keratinized tissues Reduction of wool Oxidizing agents Thioglycollate extracts Soluble derivatives of feather and other keratins The location of the cystine residues Filaments (a component) Matrix (y component) Physiochemical properties and keratinization Salt linkages Disulphide bonds Hydrogen bonds Molecular configuration in the supercontracted state The setting of hairs Cell membranes in keratinized tissues The membranes and cellular adhesion The morphology of the membranes of keratinized tissues The fate of the intracellular apparatus during keratinization The hair cuticle The medulla The residues remaining after the chemical extraction of keratins Uneven keratinization and its histological distribution Keratinized cysts and epidermal tumours Pigmentation The pigment granule The chemistry of melanization References Author Index Subject Index Preface An explanation of the sub-title of this work may not be out-of-place since it will explain at the same time the treatment of the main theme. The term molecular biology has gained currency recently; its use implies an attitude towards biology, an acceptance of the belief that biological phenomena can be related to the interaction of the molecules found in biological systems. In practice it means that the primary emphasis is placed on the determination of molecular structure by any of the means available. In its pretensions molecular biology is a generalized science; it aims to provide a common, integrating background to such special sciences as, for example, biochemistry, histology and physiology, by rendering them alike explicable in terms of molecular interaction. The name but not the subject matter is new. In the pre-war period such writers as K. H. Meyer and H. Mark, W. T. Astbury, J. D. Bernal, W. J. Schmidt, F. O. Schmitt and A. Frey-Wyssling, to mention only a few, had the objective well in mind. What is new, however, is the tempo of achievement in the post- war years; detailed structures of key biological macromolecules have been obtained and a complete coverage of cellular contents of all dimensions is possible now by means of microscopy. These achievements have lifted the dream of relating structure and function out of speculation to become a problem capable of experimental investigation. That it is still largely a project one realises quickly enough in setting out to give an account of even a simple, relatively uniform group of tissues such as the epidermis and its appendages. Thus, while this book attempts to pose the problems of keratinization consistently in molecular terms and to avoid concepts not stateable in such terms, it rather quickly degenerates into an outline of unsolved problems. Keratinization will be regarded as a development of certain primitive cellular traits adapted to serve the end of providing a protective coating to a multicellular organism. The traits emphasised are intercellular adhesion and the proliferation and stabilization of cytoplasmic protein filaments. We shall be concerned for the most part with the structure and synthesis of these filaments, with the structure of cell membranes and the nature of inter- cellular adhesion. I am grateful to Professor A. Haddow, f.r.s., Director of the Chester Beatty Research Institute, where I have found the opportunity to x ii PREFACE continue this work and to associate with many stimulating colleagues. My particular thanks are due to: Mr. M. S. C. Birbeck with whom I described here to have collaborated in much of the experimental work ; Mrs. Rex Dadd who prepared the typescript; to Mr. K. R. Moreman and Mr. M. Docherty for their careful attention to the photographic material; to Dr. P. Alexander for reading the manuscript and for his encouragement; to Dr. K. M. Rudall for reading the page proofs and Press for pointing out many shortcomings; to the staff of Pergamon unfailing attention during Ltd., in particular Mr. B. J. Adams, for their the preparation of the work for publication. E. H. Mercer 1961 : Acknowledgements My thanks are due to the following who have very kindly provided me with original photographs for plates: Mr. H. J. Woods (Plates 1 and 2), Dr. K. M. Rudall (Plate 3), Mr. M. S. C. Birbeck (Plates 5B and 10B), Dr. G. E. Rogers (Plate 16), Dr. I. Brodv (Plate 17) and Dr. I. Heiger (Plate 22A). The following publishers and societies have granted permission to reproduce