Table Of ContentEDITED BY
Roland Kaunas
Texas A&M University, College Station, USA
Assaf Zemel
Hebrew University of Jerusalem, Israel
Boca Raton London New York
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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
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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
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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.
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