Nano and Cell Mechanics E-Book

Horacio D. Espinosa

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Serie: Microsystem and Nanotechnology Series
• Sprache: Englisch

Seitenzahl: 1003

Veröffentlichungsjahr: 2012

Beschreibung

Research in nano and cell mechanics has received much attention from the scientific community as a result of society needs and government initiatives to accelerate developments in materials, manufacturing, electronics, medicine and healthcare, energy, and the environment. Engineers and scientists are currently engaging in increasingly complex scientific problems that require interdisciplinary approaches. In this regard, studies in this field draw from fundamentals in atomistic scale phenomena, biology, statistical and continuum mechanics, and multiscale modeling and experimentation. As a result, contributions in these areas are spread over a large number of specialized journals, which prompted the Editors to assemble this book.

Nano and Cell Mechanics: Fundamentals and Frontiers brings together many of the new developments in the field for the first time, and covers fundamentals and frontiers in mechanics to accelerate developments in nano- and bio-technologies.

Key features:

• Provides an overview of recent advances in nano and cell mechanics.

• Covers experimental, analytical, and computational tools used to investigate biological and nanoscale phenomena.

•  Covers fundamentals and frontiers in mechanics to accelerate developments in nano- and bio-technologies.

• Presents multiscale-multiphysics modeling and experimentation techniques.

• Examines applications in materials, manufacturing, electronics, medicine and healthcare.

Nano and Cell Mechanics: Fundamentals and Frontiers is written by internationally recognized experts in theoretical and applied mechanics, applied physics, chemistry, and biology. It is an invaluable reference for graduate students of nano- and bio-technologies, researchers in academia and industry who are working in nano and cell mechanics, and practitioners who are interested in learning about the latest analysis tools. The book can also serve as a text for graduate courses in theoretical and applied mechanics, mechanical engineering, materials science, and applied physics.

Leseprobe

Table of Contents

Microsystem and Nanotechnology Series

Title Page

Copyright

About the Editors

List of Contributors

Foreword

Series Preface

Preface

Part One: Biological Phenomena

Chapter 1: Cell–Receptor Interactions

1.1 Introduction

1.2 Mechanics of Integrins

1.3 Two-Dimensional Adhesion

1.4 Two-Dimensional Motility

1.5 Three-Dimensional Adhesion

1.6 Three-Dimensional Motility

1.7 Apoptosis and Survival Signaling

1.8 Cell Differentiation Signaling

1.9 Conclusions

References

Chapter 2: Regulatory Mechanisms of Kinesin and Myosin Motor Proteins: Inspiration for Improved Control of Nanomachines

2.1 Introduction

2.2 Generalized Mechanism of Cytoskeletal Motors

2.3 Switch I: A Controller of Motor Protein and G Protein Activation

2.4 Calcium-Binding Regulators of Myosins and Kinesins

2.5 Phospho-Regulation of Kinesin and Myosin Motors

2.6 Cooperative Action of Kinesin and Myosin Motors as a “Regulator”

2.7 Conclusion

References

Chapter 3: Neuromechanics: The Role of Tension in Neuronal Growth and Memory

3.1 Introduction

3.2 Tension in Neuronal Growth

3.3 Tension in Neuron Function

3.4 Modeling the Mechanical Behavior of Axons

3.5 Outlook

References

Part Two: Nanoscale Phenomena

Chapter 4: Fundamentals of Roughness-Induced Superhydrophobicity

4.1 Background and Motivation

4.2 Thermodynamic Analysis: Classical Problem (Hydrophobic to Superhydrophobic)

4.3 Thermodynamic Analysis: Classical Problem (Hydrophilic to Superhydrophobic)

4.4 Thermodynamic Analysis: Vapor Stabilization

4.5 Applications and Future Challenges

Acknowledgments

References

Chapter 5: Multiscale Experimental Mechanics of Hierarchical Carbon-Based Materials

5.1 Introduction

5.2 Multiscale Experimental Tools

5.3 Hierarchical Carbon-Based Materials

5.4 Concluding Remarks

References

Chapter 6: Mechanics of Nanotwinned Hierarchical Metals

6.1 Introduction and Overview

6.2 Microstructural Characterization and Mechanical Properties of Nanotwinned Materials

6.3 Deformation Mechanisms in Nanotwinned Metals

6.4 Concluding Remarks

References

Chapter 7: Size-Dependent Strength in Single-Crystalline Metallic Nanostructures

7.1 Introduction

7.2 Background

7.3 Sample Fabrication

7.4 Uniaxial Deformation Experiments

7.5 Discussion and Outlook on Size-Dependent Strength in Single-Crystalline Metals

7.6 Conclusions and Outlook

References

Part Three: Experimentation

Chapter 8: In-Situ TEM Electromechanical Testing of Nanowires and Nanotubes

8.1 Introduction

8.2 In-Situ TEM Experimental Methods

8.3 Capabilities of In-Situ TEM Applied to One-Dimensional Nanostructures

8.4 Summary and Outlook

Acknowledgments

References

Chapter 9: Engineering Nano-Probes for Live-Cell Imaging of Gene Expression

9.1 Introduction

9.2 Molecular Probes for RNA Detection

9.3 Probe Design, Imaging, and Biological Issues

9.4 Delivery of Molecular Beacons

9.5 Engineering Challenges and Future Directions

Acknowledgments

References

Chapter 10: Towards High-Throughput Cell Mechanics Assays for Research and Clinical Applications

10.1 Cell Mechanics Overview

10.2 Bulk Assays

10.3 Single-Cell Techniques

10.4 Existing High-Throughput Cell Mechanical-Based Assays

10.5 Cell Mechanical Properties and Diseases

References

Chapter 11: Microfabricated Technologies for Cell Mechanics Studies

11.1 Introduction

11.2 Microfabrication Techniques

11.3 Applications to Cell Mechanics

11.4 Conclusions

References

Part Four: Modeling

Chapter 12: Atomistic Reaction Pathway Sampling: The Nudged Elastic Band Method and Nanomechanics Applications

12.1 Introduction

12.2 The NEB Method for Stress-Driven Problems

12.3 Nanomechanics Case Studies

12.4 A Perspective on Microstructure Evolution at Long Times

References

Chapter 13: Mechanics of Curvilinear Electronics

13.1 Introduction

13.2 Deformation of Elastomeric Transfer Elements during Wrapping Processes

13.3 Buckling of Interconnect Bridges

13.4 Maximum Strain in the Circuit Mesh

13.5 Concluding Remarks

Acknowledgments

References

Chapter 14: Single-Molecule Pulling: Phenomenology and Interpretation

14.1 Introduction

14.2 Force–Extension Behavior of Single Molecules

14.3 Single-Molecule Thermodynamics

14.4 Modeling Single-Molecule Pulling Using Molecular Dynamics

14.5 Interpretation of Pulling Phenomenology

14.6 Summary

Acknowledgments

References

Chapter 15: Modeling and Simulation of Hierarchical Protein Materials

15.1 Introduction

15.2 Computational and Theoretical Tools

15.3 Case Studies

15.4 Discussion and Conclusion

Acknowledgments

References

Chapter 16: Geometric Models of Protein Secondary-Structure Formation

16.1 Introduction

16.2 Hydrophobic Effect

16.3 Prior Numerical and Coarse-Grained Models

16.4 Geometry-Based Modeling: The Tube Model

16.5 Morphometric Approach to Solvation Effects

16.6 Discussion, Conclusions, Future Work

Acknowledgments

References

Chapter 17: Multiscale Modeling for the Vascular Transport of Nanoparticles

17.1 Introduction

17.2 Modeling the Dynamics of NPs in the Macrocirculation

17.3 Modeling the NP Dynamics in the Microcirculation

17.4 Conclusions

Acknowledgments

References

Index

Microsystem and Nanotechnology Series

Series Editors:

Ron Pethig and Horacio Dante Espinosa

Nano and Cell Mechanics: Fundamentals and Frontiers,

Espinosa and Bao, January 2012

Digital Holography for MEMS and Microsystem Metrology,

Asundi, July 2011

Multiscale Analysis of Deformation and Failure of Materials,

Fan, December 2010

Fluid Properties at Nano/Meso Scale,

Dyson et al., September 2008

Introduction to Microsystem Technology,

Gerlach, March 2008

AC Electrokinetics: Colloids and Nanoparticles,

Morgan and Green, January 2003

Microfluidic Technology and Applications,

This edition first published 2013

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Library of Congress Cataloging-in-Publication Data

Nano and cell mechanics : fundamentals and frontiers / edited by Horacio D. Espinosa, Gang Bao.

p. cm. - Microsystem and nanotechnology series

Includes bibliographical references and index.

ISBN 978-1-118-46039-9 (hardback : alk. paper)

1. Biotechnology. 2. Mechanics. 3. Nanotechnology. I. Espinosa, H. D. (Horacio D.), 1957- II. Bao, Gang, 1952-

TP248.2.N353 2013

660.6-dc23

2012027597

A catalogue record for this book is available from the British Library.

ISBN: 9781118460399

About the Editors

Horacio Dante Espinosa is the James and Nancy Farley Professor of Mechanical Engineering and the Director of the Theoretical and Applied Mechanics Program at the McCormick School of Engineering, Northwestern University. He received his PhD in Applied Mechanics from Brown University in 1992. He has made contributions in the areas of dynamic failure of advanced materials, computational modeling of fracture, and multiscale experiments and simulations of micro- and nano-systems. He has published over 200 technical papers in these fields. His work has received broad attention in the media, including United Press International, NSF Discoveries, Frost and Sullivan, Science Daily, EurekAlert, Small Times, PhysOrg, Nanotechwire, Bio-Medicine, NanoVIP, Nanowerk, Genetic Engineering and Biotechnology News, Medical News Today, Materials Today, Next Big Future, Beyond Breast Cancer, AZoNano, Spektrumdirekt, and MEMSNet.

Professor Espinosa has received numerous awards and honors recognizing his research and teaching. He was elected foreign member of the Russian Academy of Engineering in 2011 and of the European Academy of Sciences and Arts in 2010, Fellow of the American Academy of Mechanics in 2001, the American Society of Mechanical Engineers in 2004, and the Society for Experimental Mechanics in 2008. He was the Timoshenko Visiting Professor at Stanford University in 2011. He received two Young Investigator Awards: the NSF-Career in 1996 and the Office of Naval Research-Young Investigator Award in 1997. He also received the American Academy of Mechanics (AAM) 2002-Junior Award, the Society for Experimental Mechanics (SEM) 2005 HETENYI Award, the Society of Engineering Science (SES) 2007 Junior Medal, and the 2008 LAZAN award from the Society for Experimental Mechanics. He currently serves as Founding Principal Editor of MRS Communications and co-editor of the Wiley Book Series in Microsystems and Nanotechnologies. He also served as Editor-in-Chief of the Journal of Experimental Mechanics and Associate Editor of the Journal of Applied Mechanics. He is the 2012 President of the Society of Engineering Science and a member of the US National Committee for Theoretical and Applied Mechanics.

Professor Espinosa is also the founder and chief scientific officer of iNfinitesimal LLC, a nanotechnology company developing robust next-generation nanoscale devices, scalable nanomanufacturing tools, and microdevices for single-cell transfection and analysis.

Dr Gang Bao is Robert A. Milton Chair of Biomedical Engineering and a College of Engineering Distinguished Professor in the Department of Biomedical Engineering, Georgia Institute of Technology and Emory University. He is Director of the Center for Translational Cardiovascular Nanomedicine, an NIH/NHLBI Program of Excellence in Nanotechnology (PEN) at Georgia Tech and Emory University, and Director of Nanomedicine Center for Nucleoprotein Machines, an NIH Nanomedicine Development Center (NDC) at Georgia Tech, and Director of the Center for Pediatric Nanomedicine at Children's Healthcare of Atlanta and Georgia Tech. Dr Bao received his undergraduate and Master's degrees from Shandong University in China and his PhD from Lehigh University in the USA. Dr Bao is a Fellow of the American Association of Advancement in Science (AAAS), a Fellow of the American Society of Mechanical Engineers (ASME), a Fellow of the American Physical Society (APS), and a Fellow of the American Institute for Medical and Biological Engineering (AIMBE).

Dr Bao's current research is focused on the development of nanotechnology and biomolecular engineering tools for biological and disease studies, including molecular beacons, magnetic nanoparticle probes, quantum dot bioconjugates, protein tagging/targeting methods, and engineered nucleases. These approaches have been applied to the diagnosis and treatment of cancer and cardiovascular disease, viral infection detection, and the development of gene correction approaches for treating single-gene disorders.

List of Contributors

Wylie W. Ahmed

Department of Mechanical Science & Engineering, University of Illinois, USA

Rodrigo A. Bernal

Department of Mechanical Engineering, Northwestern University, USA

Graham Bratzel

Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, USA

Department of Mechanical Engineering, Massachusetts Institute of Technology, USA

Markus J. Buehler

Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, USA

Paolo Decuzzi

Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, USA

Mauro Ferrari

Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, USA

Tobin Filleter

Department of Mechanical and Industrial Engineering, University of Toronto, Canada

Daniel A. Fletcher

Department of Bioengineering, University of California at Berkeley, USA

Graduate Group in Biophysics, University of California, Berkeley, California, USA

Ignacio Franco

Department of Chemistry, Northwestern University, Evanston, USA

Huajian Gao

School of Engineering, Brown University, USA

Tristan Giesa

Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, USA

Department of Mechanical Engineering, RWTH Aachen University, Germany

Julia R. Greer

California Institute of Technology, USA

Hendrik Hansen-Goos

Department of Geology and Geophysics, Yale University, USA

Shaolie S. Hossain

Department of Translational Imaging and Department of Nanomedicine, The Methodist

Hospital Research Institute, USA

Yonggang Huang

Department of Mechanical Engineering, USA

Department of Civil and Environmental Engineering, Northwestern University, USA

Thomas J.R. Hughes

Institute for Computational Engineering and Sciences, The University of Texas at Austin, USA

Adrian M. Kopacz

Department of Mechanical Engineering, Northwestern University, USA

Wilbur A. Lam

Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta and Emory University School of Medicine

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA

Sei-Young Lee

Samsung—Global Production Technology Center, Korea

Tae-Rin Lee

Department of Mechanical Engineering, Northwestern University, USA

Xiaoyan Li

School of Engineering, Brown University, USA

Man C. Leong

NUS Graduate School for Integrative Sciences and Engineering, Singapore

David Lepzelter

Department of Biomedical Engineering, Boston University, USA

Ju Li

Department of Nuclear Science and Engineering

Department of Materials Science and Engineering, Massachusetts Institute of Technology, USA

Seth Lichter

Department of Mechanical Engineering, Northwestern University, USA

Chwee T. Lim

Mechanobiology Institute, National University of Singapore, Singapore

Department of Bioengineering, Singapore

Wing Kam Liu

Department of Mechanical Engineering, Northwestern University, USA

David R. Myers

Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta and Emory University School of Medicine, USA

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA

Mohammad Naraghi

Texas A&M University, USA

Neelesh A. Patankar

Department of Mechanical Engineering, Northwestern University, USA

Jagannathan Rajagopalan

Arizona State University, USA

Mark A. Ratner

Department of Chemistry, Northwestern University, USA

Sarah Rice

Department of Cell and Molecular Biology, Northwestern University Medical School, USA

John A. Rogers

Department of Materials Science and Engineering, Department of Mechanical Science and Engineering, Department of Electrical and Computer Engineering, Department of Chemistry, and Frederick Seitz Materials Research Laboratory, University of Illinois, USA

Taher A. Saif

Department of Mechanical Science and Engineering, University of Illinois, USA

George C. Schatz

Department of Chemistry, Northwestern University, USA

Jizhou Song

Department of Mechanical and Aerospace Engineering, University of Miami, USA

Alireza Tofangchi

Department of Mechanical Science and Engineering, University of Illinois, USA

Andrew Tsourkas

Department of Bioengineering, University of Pennsylvania, USA

Sri Ram K. Vedula

Mechanobiology Institute, National University of Singapore, Singapore

Shuodao Wang

Department of Mechanical Engineering, Northwestern University, USA

Brian Wile

Department of Biomedical Engineering, Georgia Institute of Technology and Emory, USA

Jianliang Xiao

Department of Mechanical Engineering, University of Colorado, USA

Sidney Yip

Department of Nuclear Science and Engineering

Department of Materials Science and Engineering, Massachusetts Institute of Technology, USA

Muhammad Zaman

Department of Biomedical Engineering, Boston University, USA

Yongjie Zhang

Department of Mechanical Engineering, Carnegie Mellon University, USA

Ting Zhu

Woodruff School of Mechanical Engineering, Georgia Institute of Technology, USA

Foreword

The articles included in this volume, compiled by Dr. Gang Bao and Dr. Horacio Espinosa, can be viewed as a benchmark along the evolutionary path of what our scholarly community views as its “field of research.” Consequently, the preparation of this foreword provides an opportunity to lend perspective to the book as a whole.

Among senior researchers, it is common for one to feel that their own field reached its pinnacle when they were young, but that it has been suffering a steady decline ever since. The contents of this book will surely dissuade anyone involved in research on the mechanics of hard or soft materials from harboring such a view! When I was first exposed to the field of mechanics nearly a half century ago, the focus was on the mathematical solution of boundary-value problems, either exactly or approximately, and this point of view pervaded graduate courses. There was a small but active experimental community involved in measurement of deformation with strain gages, photoelastic strategies, and, occasionally, optical interference techniques. At about this time, a few visionaries in the community demonstrated to the Department of Defense that there was enormous potential for advances in engineering and technology through more effective exploitation of materials; as a result, a number of national materials research laboratories were es- tablished at universities around the country, with mechanics taking a central role in a number of these centers.

As a result, the organizational barriers between mechanics and materials were gradually overcome, and many of us opted to align our research efforts with the new area of mechanics of materials. Computational methods joined analytical and experimental methods as core activities, and advances in both fabrication and characterization of experimental samples introduced us to the exciting and complex world of deformation of materials at small size scales. Graduate education became much more diverse with the integration of mechanics and materials science, and the introduction of computation provided a powerful means for describing the behavior of materials quantitatively and for addressing issues of competition among potential mechanisms of deformation or failure.

The important role of mechanical stress on thin film materials and other small structures, which are largely intended for nonmechanical functions, arose as a focus of research efforts. Connections between macroscopic fracture strength of materials and the details of material microstructure were established, the inuence of plastic strain localization due to material instability in deformation was quantified, and the role of dislocation formation or crystallographic twinning or other phase transformations on the nonmechanical functional characteristics of materials was established, for example. The topics became important focal issues for graduate courses in the field, and a greatly increased range and sophistication in sample preparation and diagnostic tools became available in laboratories. This was the prevailing atmosphere in the field at about the time the editors of this volume emerged as active members of the community.

The field of mechanics of materials had changed fundamentally, having formed a focus on the physical and chemical aspects of phenomena as much as the mathematical 1 aspects, computation became an indispensable methodology, and methods of laboratory sample fabrication, observational techniques, and data analysis created opportunities that seemed unattainable only a short time earlier. Researchers could now apply this suite of tools to examine and quantitatively understand the behavior of materials at an even smaller scale. It was soon found that the mechanisms of biological functions, which before had been identified through the long and painstaking process of assaying, could be observed directly.

As we gaze forward in time from the current frontiers of mechanics research, we see that the “landscape” to be traversed is less well defined than it had been in the past. Mechanical phenomena at the smaller size scales are often inseparable from chemical, biological, and/or quantum mechanical inuences, and the rules governing behavior are no longer certain. Consequently, instead of reliance on precise analytical and/or numerical analyses, we must examine data obtained through brief glimpses of the nano-world in the laboratory or seek guidance from the global principles of thermodynamics. Although these aspects loom as impediments to progress, the task of overcoming them lends a sense of timeliness and excitement to the mechanics research field overall.

As illustrations of the broad consequences of these developments, this volume includes a report on the inuence of mechanical tension on neuronal growth and memory in the human brain. Another article reports on direct measurement of the mechanical properties of cylindrical test samples with diameters as small as 50 nm. There is a discussion of the connections between mechanical properties of cells and human disease, as well as a quantitative description of what can be learned by separating a pair of chemically bound molecules under controlled conditions, plus many others. We can learn a great deal from study of the articles individually, of course. It is equally important to consider their collective significance as an indicator of the excitement, broad relevance, and future promise of our field.

L. B. FreundChampaign, IL, USA

Series Preface

Books in this series are intended, through scholarly works of the highest quality, to serve researchers and scientists wishing to keep abreast of advances in the expanding field of nano- and micro-technology. These books are also intended to be a rich interdisciplinary resource for teachers and students of specialized undergraduate and postgraduate courses.

A recent example includes the university textbook Introduction to Microsystem Technology by Gerlach and Dötzel, covering the design, production and application of miniaturised technical systems from the viewpoint that for engineers to be able to solve problems in this field they need to have interdisciplinary knowledge over several areas as well as the capability of thinking at the system level. In their book Fluid Properties at Nano/Meso Scale, Dyson et al take us step by step through the fluidic world bridging the nanoscale, where molecular physics is required as our guide, and the microscale where macro continuum laws operate. Jinghong Fan in Multiscale Analysis of Deformation and Failure of Materials provides a comprehensive coverage of a wide range of multiscale modeling methods and simulations of the solid state at the atomistic/nano/submicron scales and up through those covering the micro/meso/macroscopic scale. Most recently Digital Holography for MEMS and Microsystem Metrology, edited by Anand Asundi, offers timely contributions from experts at the forefront of the development and applications of this important technology.

In this book Professors Espinosa and Bao have assembled, through their own inputs and those of 47 other experts of their chosen fields of endeavour, 17 timely and exciting chapters that must surely represent the most comprehensive coverage yet presented of all aspects of the mechanics of cells and biomolecules. The editors have ensured, through the careful choice of the contents and their order of presentation in four main sections, that we have a coherent presentation of the extraordinary wide range of interdisciplinary components that make up this exciting frontier in applied mechanics. Apart from their clarity of presentations, all the authors have adopted a pedagogical style of writing, making much of this book's content suitable for inclusion in undergraduate and postgraduate courses. A foreword, both historic and insightful, has also been composed by Professor L Ben Freund - whose own contributions to various aspects of the mechanics of biological materials will have influenced the thinking of many of the contributors to this excellent book.

Ronald PethigProfessor of BioelectronicsUniversity of Edinburgh, UK

Preface

In the past decade, nano- and bio-technologies have received unprecedented attention from the government and private sectors as well as the general public owing to their potential in impacting our lives through fundamental discoveries, innovation, and translational research efforts. Engineers and applied scientists have played a major role in developing these technologies and made essential contributions to applying them to a wide range of industries, including manufacturing, healthcare, agriculture, energy, and defense.

Consistent with this, research in nano-mechanics and the mechanics of living cells and biomolecules has become a frontier in applied mechanics. Studies in this exciting research area are interdisciplinary in nature and draw engineers and scientists from a diverse range of fields, including nanoscale science and engineering, biology, statistical and continuum mechanics, and multiscale-multiphysics modeling and experimentation. As a result, original contributions to the development of nano- and cell-mechanics are published in a large number of specialized journals, which prompted us in editing this book. The book documents, for the first time, many recent developments in nano- and cell-mechanics and showcases emergent new research areas and techniques in engineering that are at the boundaries of mechanics, materials science, chemistry, biology, and medicine. As such, this book allows those entering the field a quick overview of experimental, analytical, and computational tools used to investigate biological and nanoscale phenomena. This book may also serve as a textbook for a graduate course in theoretical and applied mechanics, mechanical engineering, materials science, and applied physics.

The 17 chapters in this book are organized in four sections: (1) Biological phenomena, (2) Nanoscale phenomena, (3) Experimentation, and (4) Modeling. The biological phenomena section covers cell–receptors interactions, regulatory molecular motors, and the role of tension in neuronal growth and memory. The nanoscale phenomena section examines superhydrophobicity, multiscale mechanics of hierarchical carbon-based materials, mechanics of twinning in hierarchical metals, and size-dependent strength in single-crystalline metallic nanostructures. The experimentation section discusses in-situ electron characterization of nanomaterials, the engineering of nano-probes for live-cell imaging of gene expression, high-throughput cell mechanic assays for research and clinical applications, and microfabrication technologies for cell mechanics studies. The last section, modeling, spans a number of methods and applications: atomistic reaction pathway sampling, mechanics of curvilinear electronics, single molecular pulling, modeling of hierarchical protein materials, geometric models of protein secondary structure formation, and multiscale modeling for the vascular transport of nanoparticles.

We would like to thank Ben Freund for providing a historic perspective and an inspiring Foreword. Likewise, we are particularly thankful to all authors for providing authoritative and comprehensive reviews of recent advances in their field of expertise. We would also like to thank the Wiley staff, Anne Hunt and Tom Carter in particular, for guidance and assistance over the preparation of this book. Their experience and professionalism was essential to this project. A special thanks is also due to our assistants, Andrea DeNunzio and Amy Tang, who communicate regularly with the authors to collect all the needed materials.

Horacio D. Espinosa and Gang Bao

Part One

Biological Phenomena

Chapter 1

Cell–Receptor Interactions

David Lepzelter and Muhammad Zaman

Boston University, USA

1.1 Introduction

One of the most basic functions of the cells of a multicellular organism is to stay attached to the rest of the organism. This is called cell adhesion. It is not a trivial task, especially since different kinds of cells require different levels of attachment. Further, in complex organisms some cells must be able to change their levels of attachment based on their local environments: platelets must transform from almost completely nonadhesive to adhesive when they reach the site of an injury, and white blood cells must recognize cell types and respond by attaching to (and attacking) foreign materials and infected cells. Further still, sensing the levels and types of attachment can be vital to extremely important decision-making pathways in cells, such as those related to apoptosis (cell death) and cell differentiation. The precise mechanisms by which these processes occur are varied, and while they are still under study, much about them is known.

In general, cells attach to extracellular objects or other cells using proteins that are imbedded in their membranes. Transmembrane proteins have at least one hydrophobic portion, or membrane domain, which anchors them in the membrane. They also have hydrophilic portions, which interact with the cytosol (cytoplasmic domains) or cell environment (extracellular domains). These proteins often serve as sensors, binding to molecules with their extracellular regions and passing along information about the environment to the inside of the cell via configuration changes; this is called outside-in signaling. Some reverse the process, providing an extracellular signal regarding conditions inside the cell, and some perform both functions. A few bind strongly enough to extracellular materials or other cells' extracellular protein domains that they remain attached even with significant forces pulling them away. These form the basis of cell adhesion.

Among these adhesion proteins are immunoglobulins, selectins, cadherins, and integrins. This chapter will briefly discuss all of them, but will focus on the primary agent in cell adhesion to the extracellular matrix: integrins.

Immunoglobulins, or antibodies, are used by the immune systems of vertebrates to identify and eliminate infection and cell malfunction. They do this through selective and customized binding; an immune-related cell will find a marker (often a protein) on a foreign object and customize an antibody in such a way that it binds preferentially to that marker based largely on its shape [1]. This will allow identification of proper targets for immune response, and begin the immune response appropriate for the object in question.

Selectins are adhesion molecules specific to leukocytes, platelets, and endothelial cells. They exhibit very fast binding, allowing them to act similar to a braking system on moving cells when they have reached a site of bleeding or infection [2].

Cadherins are direct cell–cell adhesion proteins. They generally operate by binding to each other; cadherins on one cell will bind to cadherins on another. There are a number of different varieties (e.g., E-cadherin), many of which preferentially bind to cadherins of the same type [3]. Members of the cadherin superfamily are involved in cell signaling, adhesion, recognition, communication, morphogenesis, and angiogenesis [4].

Integrins, the main focus of this chapter, are found in animals and bind primarily to various proteins which are part of a ubiquitous biological scaffolding in animals called the extracellular matrix. The form of integrins commonly found is actually a heterodimer: an α protein and a β protein each with an extracellular domain, a membrane domain, and a cytoplasmic domain. The two interact with each other to make the overall form of the integrin functional. There are currently 18 known varieties of the α subunit and eight known varieties of the β, making 24 distinct viable combinations [5].