EDITED BY Roland Kaunas Texas A&M University, College Station, USA Assaf Zemel Hebrew University of Jerusalem, Israel Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2015 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Version Date: 20140904 International Standard Book Number-13: 978-1-4665-5382-8 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the valid- ity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or uti- lized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopy- ing, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http:// www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Contents Preface ............................................................................................................................................vii Editors ..............................................................................................................................................ix Contributors ....................................................................................................................................xi 1. Active Mechanics of the Cytoskeleton ...............................................................................1 José Alvarado and Gijsje Koenderink 2. Mechanobiology of the Cell Membrane ..........................................................................35 Peter J. Butler, Hari S. Muddana, and Sara Farag 3. Cellular Reconstitution of Actively Self-Organizing Systems ...................................63 Orit Siton-Mendelson, Barak Gilboa, Yaron Ideses, and Anne Bernheim-Groswasser 4. Structural and Dynamical Hierarchy of Fibrillar Collagen ......................................101 Xiaojing Teng and Dr. Wonmuk Hwang 5. Cell–Matrix and Cell–Cell Mechanical Interactions ..................................................119 Assaf Zemel and Ralf Kemkemer 6. Dynamic Stress Fiber Reorganization on Stretched Matrices ..................................149 Roland Kaunas 7. Mechanics of Cell-Seeded ECM Scaffolds ....................................................................173 Guy M. Genin and Elliot L. Elson 8. Cell Motility in 3D Matrices ............................................................................................197 Yasha Sharma and Muhammad H. Zaman 9. Collective Cell Migration ..................................................................................................219 Nir S. Gov 10. Connective Tissue Development .....................................................................................239 Albert Harris 11. Cellular Forces in Morphogenesis ..................................................................................259 Larry A. Taber 12. Mechanics of Tissue Morphogenesis .............................................................................285 Michael J. Siedlik and Celeste M. Nelson v vi Contents 13. Continuum Physics of Tumor Growth ...........................................................................309 Kristen L. Mills, Shiva Rudraraju, Ralf Kemkemer, and Krishna Garikipati 14. Cell Force–Mediated Collagen Remodeling in Cancer Metastasis ..........................329 Paolo P. Provenzano Index .............................................................................................................................................351 Preface The field of cell mechanics has seen extensive development over the past few decades. New technologies have been invented to finely manipulate the mechanical and geometri- cal characteristics of the cellular environment, to apply precise doses of mechanical load, and to image the induced cellular response at both subcellular and molecular levels. Mechanical stimulation has been shown to be as potent and significant as chemical stimuli in affecting virtually all aspects of cell function. This includes effects on individual cell processes such as adhesion, migration, division, and gene expression regulation, as well as on collective behaviors such as cell–cell interactions, matrix remodeling, morphogen- esis, and disease. A comprehensive understanding of the complex mechanical interplay between cells and their surrounding extracellular matrix is a multiscale problem in time and space, ranging from the molecular level and millisecond time scale up to the multicell or tissue levels involving a time scale of days to months. This book brings together experts in the field of cell mechanics to summarize cutting- edge research at the molecular, cellular, and tissue levels with a focus on cell–matrix interactions. At each length scale, key experimental observations and corresponding quantitative theoretical models are presented. The book is organized in three sections that correspond to those three hierarchical levels. In Section I, which is focused on the molecular level, the passive and active mechanical properties of cytoskeletal polymers and associated motor proteins are discussed along with the behavior of polymer net- works in Chapters 1 and 3. The mechanical properties of the cell membrane are presented in Chapter 2, with an emphasis on membrane protein activation caused by membrane forces. The hierarchical organization of collagen fibrils is discussed in Chapter 4, reveal- ing that a delicate balance exists between specific and nonspecific interactions to result in a structure with semicrystalline order as well as loose associations. Section II focuses on mechanics at the cellular level. In Chapter 5, the roles of matrix mechanical properties on cell adhesion and function are presented along with different mechanical mecha- nisms of cell–cell interactions. The effects of mechanical loading on cell cytoskeletal remodeling are presented in Chapter 6, summarizing various modeling approaches that explain possible mechanisms regulating the alignment of actin stress fibers in response to stretching. Mechanical testing of cell-populated collagen matrices is described in Chapter 7, along with theory relating the passive and active mechanical properties of the engineered tissues. Chapters 8 and 9 focus on cell migration behavior in 3-D matrices and in collective cell motility. Section III of the book concerns cellular mechanics at the tissue level. Starting with a summary of the pioneering studies of cell–matrix mechanics by Albert Harris, Chapter 10 is devoted to the role of mechanics in cartilage develop- ment. Chapters 11 and 12 describe the roles of both cellular and external forces on tis- sue morphogenesis. Finally, the roles of mechanical forces on tumor growth and cancer metastasis are presented in Chapters 13 and 14, respectively. These chapters are not meant to provide a complete summary of current research in the field, but instead they provide a thorough description of the roles of mechanical forces in cell and tissue biology. Despite the range of concepts presented, the material in each chap- ter relates to that of the others. For example, tumor cell metastasis involves cell–cell inter- actions, cell migration in 3-D tissues, and collective cell migration. Similar connections can vii viii Preface be drawn between tissue morphogenesis and cell behavior in mechanically loaded tissues. All of these phenomena depend on the mechanical properties of active cytoskeletal poly- mer networks, cell membranes, and collagen fibrils. It is our hope that specific examples described herein, along with descriptions of associated theoretical models, will inspire future development of multiscale models that elucidate the roles of mechanical forces in cell–matrix biology. Editors Roland Kaunas is an associate professor of biomedical engineering and the director of the Cell Mechanobiology Laboratory at Texas A&M University. He earned his BS in chemical engineering at the University of Wisconsin, his MS in biomedical engineering at Northwestern University, and his PhD in bioengineering with Shu Chien from the University of California, San Diego. He joined the faculty at Texas A&M in 2005, where his research focuses on experimental and computational modeling of cell reorganization and mechanotransduction in response to matrix stretching, fluid shear stress mecha- notransduction in sprouting angiogenesis, and the development of collagen-based scaf- folds for adult stem cell delivery for osteoregenerative therapies. His research is funded by the National Institutes of Health (NIH), National Science Foundation, American Heart Association, and the Center for the Advancement of Science in Space. Assaf Zemel is a senior lecturer of theoretical biophysics and head of the theoretical bio- physics laboratory at the Institute of Dental Sciences at the Hebrew University of Jerusalem. He is also affiliated with the Fritz Haber Research Center for Molecular Dynamics at the Center for Bioengineering of the Hebrew University. Assaf earned his PhD in theoretical chemistry from the Hebrew University. He then shifted to the field of cell mechanics for his postdoctoral research at the Weizmann Institute and the University of California at Davis. His current research focuses on understanding the physical mechanisms underly- ing the morphology, dynamics and internal structure of cells, and the mechanics of cell– cell interactions and morphogenesis. ix