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Biological Physics of the Developing Embryo

During development, cells and tissues undergo dynamic changes in pattern and form that employ a wider range of physical mechanisms than at any other time during an organism's life. Biological Physics of the Developing Embryo presents a framework within which physics can be used to analyze these biological phenomena.

   Written to be accessible to both biologists and physicists, major stages and components of biological development are introduced and then analyzed from the viewpoint of physics. The presentation of physical models requires no mathematics beyond basic calculus. Physical concepts introduced include diffusion, viscosity and elasticity, adhesion, dynamical systems, electrical potential, percolation, fractals, reaction–diffusion systems, and cellular automata.

   With full-color figures throughout, this comprehensive textbook teaches biophysics by application to developmental biology and is suitable for graduate and upper-undergraduate courses in physics and biology.

GABOR FORGACS is George H. Vineyard Professor of Biological Physics at the University of Missouri, Columbia. He received his Ph.D. in condensed matter physics from the Roland Eötvös University in Budapest. He made contributions to the physics of phase transitions, surface and interfacial phenomena and to statistical mechanics before moving to biological physics, where he has studied the biomechanical properties of living materials and has modeled early developmental phenomena. His recent research on constructing models of living structures of prescribed geometry using automated printing technology has been the topic of numerous articles in the international press.

Professor Forgacs has held positions at the Central Research Institute for Physics, Budapest, at the French Atomic Energy Agency, Saclay, and at Clarkson University, Potsdam. He has been a Fulbright Fellow at the Institute of Biophysics of the Budapest Medical University and has organized several meetings on the frontiers between physics and biology at the Les Houches Center for Physics. He has also served as advisor to several federal agencies of the USA on the promotion of interdisciplinary research, in particular at the interface of physics and biology. He is a member of a number of professional associations, such as The Biophysical Society, The American Society for Cell Biology, and The American Physical Society.

STUART A. NEWMAN is Professor of Cell Biology and Anatomy at New York Medical College, Valhalla, New York. He received an A.B. from Columbia University and a Ph.D. in Chemical Physics from the University of Chicago. He has contributed to several scientific fields, including developmental pattern formation and morphogenesis, cell differentiation, the theory of biochemical networks, protein folding and assembly, and mechanisms of morphological evolution. He has also written on the philosophy, cultural background and social implications of biological research.

Professor Newman has been an INSERM Fellow at the Pasteur Institute, Paris, and a Fogarty Senior International Fellow at Monash University, Australia. He is a co-editor (with Brian K. Hall) of Cartilage: Molecular Aspects (CRC Press, 1991) and (with Gerd B. Müller of Origination of Organismal Form: Beyond the Gene in Developmental and Evolutionary Biology (MIT Press, 2003). He has testified before US Congressional committees on cloning, stem cells, and the patenting of organisms and has served as a consultant to the US National Institutes of Health on both technical and societal issues.

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Biological Physics of the
Developing Embryo

Gabor Forgacs

University of Missouri

and

Stuart A. Newman

New York Medical College

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CAMBRIDGE UNIVERSITY PRESS
Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo

Cambridge University Press
The Edinburgh Building, Cambridge CB2 2RU, UK
Published in the United States of America by Cambridge University Press, New York

www.cambridge.org
Information on this title: www.cambridge.org/9780521783378

© G. Forgacs and S. A. Newman 2005

This publication is in copyright. Subject to statutory exception
and to the provisions of relevant collective licensing agreements,
no reproduction of any part may take place without
the written permission of Cambridge University Press.

First published 2005

Printed in the United Kingdom at the University Press, Cambridge

A catalog record for this publication is available from the British Library

Library of Congress Cataloging in Publication data

ISBN-13 978-0-521-78337-8 hardback
ISBN-10 0-521-78337-2 hardback

Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate.

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Contents

		Acknowledgments	page vii
		Introduction: Biology and physics	1
1		The cell: fundamental unit of developmental systems	6
		The eukaryotic cell	6
		Diffusion	8
		Osmosis	15
		Viscosity	16
		Elasticity and viscoelasticity	21
		Perspective	22
2		Cleavage and blastula formation	24
		The cell biology of early cleavage and blastula formation	24
		Physical processes in the cleaving blastula	29
		Physical models of cleavage and blastula formation	39
		Perspective	50
3		Cell states: stability, oscillation, differentiation	51
		Gene expression and biochemical state	52
		How physics describes the behavior of a complex system	53
		Oscillatory processes in early development	57
		Multistability in cell-type diversification	63
		Perspective	76
4		Cell adhesion, compartmentalization, and lumen formation	77
		Adhesion and differential adhesion in development	78
		The cell surface	80
		Cell adhesion: specific and nonspecific aspects	81
		The kinetics of cell adhesion	84
		Differential adhesion of embryonic tissues	90
		The physics of cell sorting	95
		Perspective	97
5		Epithelial morphogenesis: gastrulation and neurulation	99
		Physical properties of epithelia	100
		Gastrulation	108
		Convergence and extension	117
		Neurulation	122
		Perspective	128
		Appendix: Linear stability analysis	128
6		Mesenchymal morphogenesis	131
		Development of the neural crest	134
		The extracellular matrix: networks and phase transformations	138
		Mesenchymal condensation	149
		Perspective	154
7		Pattern formation: segmentation, axes, and asymmetry	155
		Basic mechanisms of cell pattern formation	157
		Segmentation	162
		Epithelial patterning by juxtacrine signaling	168
		Mesoderm induction by diffusion gradients	171
		Reaction–diffusion systems	173
		Control of axis formation and left–right asymmetry	177
		Perspective	187
8		Organogenesis	188
		Development of the cardiovascular system	190
		Fractals and their biological significance	197
		Branching morphogenesis: development of the salivary gland	203
		Vertebrate limb development	210
		Perspective	222
9		Fertilization: generating one living dynamical system from two	223
		Development of the egg and sperm	224
		Interaction of the egg and sperm	233
		Propagation of calcium waves: spatiotemporal encoding of postfertilization events	236
		Surface contraction waves and the initiation of development	242
		Perspective	247
10		Evolution of developmental mechanisms	248
		The physical origins of developmental systems	249
		Analyzing an evolutionary transition using physical concepts: segmentation in insects	256
		The evolution of developmental robustness	262
		Perspective	272
		Glossary	273
		References	291
		Index	327

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Acknowledgments

The writing of this text, addressed simultaneously to biologists and physicists, presented us with many challenges. Without the help of colleagues in both fields the book would still be on the drawing board. Of the many who advised us, made constructive remarks, and provided suggestions on the presentation of complex issues, we wish to thank particularly Mark Alber, Daniel Ben-Avraham, Andras Czirók, Scott Gilbert, James Glazier, Tilmann Glimm, Michel Grandbois, George Hentschel, Kunihiko Kaneko, Ioan Kosztin, Roeland Merks, Gerd Müller, Vidyanand Nanjundiah, Adrian Neagu, Olivier Pourquié, Diego Rasskin-Gutman and Isaac Salazar-Ciudad. Commentary from students was indispensable; in this regard we received invaluable help from Richard Jamison, an undergraduate at Clemson University, and Yvonne Solbrekken, an undergraduate at the University of Missouri, Columbia, who read most of the chapters.

   We thank the members of our laboratories for their patience with us during the last five years. Their capabilities and independence have made it possible for us to pursue our research programs while writing this book. Gabor Forgacs was on the faculty of Clarkson University, Potsdam, NY, when this project was initiated, and some of the writing was done while he was a visiting scholar at the Institute for Advanced Study of the Collegium Budapest. Stuart Newman benefited from study visits to the Indian Institute of Science, Bangalore, the Konrad Lorenz Institute, Vienna, and the University of Tokyo-Komaba, in the course of this work.

   In a cross-disciplinary text such as this one, graphic materials are an essential element. Sue Seif, an experienced medical illustrator, was, like us, new to the world of textbook writing. Our interactions with her in the design of the figures in many instances deepened our understanding of the material presented here. Any reader who accompanies us across this difficult terrain will appreciate the freshness and clarity of Sue’s visual imagination.

   Harry Frisch introduced the authors to one another more than a quarter century ago and thought that we had things to teach each other. Malcolm Steinberg, a valued colleague of both of us, showed the way to an integration of biological and physical ideas. Judith Plesset, our program officer at the National Science Foundation, was instrumental in fostering our scientific collaboration during much of the intervening period, when many of the ideas in this book were gestated. We are grateful to each of them and for the support of our families.

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