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INTEGRATED
NANO-
BIOMECHANICS
INTEGRATED
NANO-
BIOMECHANICS
Edited by
TAKAMI YAMAGUCHI
TAKUJI ISHIKAWA
YOHSUKE IMAI
Elsevier
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Notices
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Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using
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material herein.
ISBN: 978-0-323-38944-0
xiii
PREFACE
Takami Yamaguchi
Takuji Ishikawa
Yohsuke Imai
xv
INTRODUCTION
1
Takami Yamaguchi
Biomedical Engineering, Tohoku University, Sendai, Japan
large and complex protein, are not alive. If we accept the fact, we
will be obliged to consider that the relationship or interactions
between these components of the cell are life, and this is the rea-
son why the nanoscale biomechanics is necessary. After the estab-
lishment of molecular biology, particularly so-called omics
studies, complex nature of the biological existence is exceedingly
pronounced. However, not the appreciation of complex nature
nor its massive statistical analysis without guiding principle leads
to truly comprehensive understanding of life. In this sense, nano-
scale interactions between subnanoscale substances in the cell,
which our nanoscale study is aimed, are the key issue of the
biology.
Biology of the cell revealed that every cell has an ability to sense
and quantitate the mechanical environments surrounding it. This
understanding is now widely possessed by researchers, and thus,
the field of the study is called mechanobiology. Not only mechan-
ics is important in the analysis of mechanical response of special
cells such as endothelium of the vascular wall, but also the study
of many different kinds of cells should be carried out. Mechanical
receptor proteins or mechanoreceptor channels are widely stud-
ied in sensing cells. These receptor-mediated mechanisms may be
a part of mechanobiological processes. However, we need to con-
sider the whole structure of the cell that responds to mechanical
stimuli and detailed mechanism. Again, this is the level of nano-
biomechanics, and further study, not merely molecular research,
is now necessary.
In the multicellular organism including us, no cells move and
work independently, except blood cells and germ cells, such as
sperm and egg. Of those exceptions, egg is literally single, and
others are collective. In order to analyze and understand the col-
lective motion of those cells, single-cell motion should be exam-
ined first. Of those cells of collective motion, erythrocyte or red
blood cells (RBCs) and platelets are thought of as purely passive
because they have no motive element. Leucocytes or WBCs and
sperms are active in their motion. However, their motility has
quite different timescale. The timescale of spermatic motion is
an order of 1–10 3 s, while motion of leucocytes is almost passive
when they are in the blood flow and become motile after they stick
to the vascular wall. Its motion on and through the vascular wall
could be an order of 1–10 3 s or longer. In the case of sperm, their
interaction to each other may not be important. However, it is
shown that sperms move collectively. Interaction is very impor-
tant in the case of blood cells. RBCs, particularly due its concen-
tration in the blood, must be eventually analyzed through their
multiple-body interactions. WBC motion must be analyzed with
Chapter 1 INTRODUCTION 5
their interactions not with each other but with their interactions
with the erythrocytes in the blood flow and with endothelial cells
when they reside adjacent to the wall. Platelets are smaller than
those blood cells, and their motion is strongly influenced by the
RBC. Formation of thrombosis and hemostasis should be under-
stood under this condition. Consequently, motion and character-
istics of the multicellular fluid such as the blood must be
examined through the single-cell mechanics, and their collective
nature should be reconstructed by the collective motion of the
unit component. This is an attempt to reorganize the rheology
of the physiological fluids and is now possible to discuss this
thanks to huge-scale computation.
Traditionally, particularly in the field of engineering, mechan-
ics studies are divided into some subfields, typically fluid
mechanics, solid mechanics, thermodynamics and transport phe-
nomena, mechanical dynamics, and electromagnetics. However,
we have to place a stress on the fact that none of the biological
phenomenon can be analyzed by only one of those subspecific
measures. For example, production, transmission, and transduc-
tion of biological signals are governed by the interaction of the
electric field and electromagnetic transformation of ion channel
protein molecules and the diffusion of molecules in the synaptic
gap. This typically ends up in the contraction of muscle to pro-
duce macroscopic motion of the body. Conventionally, this pro-
cess is not studied from the mechanical viewpoint. However,
whole process is based on mechanics. Electric excitement and
transmission of the pulse are sequential processes of the electro-
magnetic deformation of the channel protein, and final transmis-
sion of the excitement is based on the axonal transport of the
material from the neuronal cell body to the synapse. Nanoscale
biomechanics should be involved in the study of whole physiology
of the living system as such.
Fluid-solid interaction is another problem of intermechanics
or combined studies. As shown later in this book, a number of bio-
logical systems are composed of solid components and fluid com-
ponents. Simplest cell in the whole body, the RBC, is a good
example. It has no intracellular solid components such as the
nucleus and the mitochondria, but just a thick solution of hemo-
globin occupies the cell. Our analysis revealed, nevertheless, that
the stiffness of the cell membrane and the viscosity of the intra-
cellular fluid relative to that of surrounding fluid, which is the
plasma, greatly affect the deformation and motion of the RBC
and therefore total blood flow in the smaller vasculature. This
is a typical example showing the necessity of the fluid-solid
interaction studies, though the theoretical difficulty and the
6 Chapter 1 INTRODUCTION
CHAPTER OUTLINE
2.1 Behavior of Capsules in Flow 10
2.1.1 Governing Equations and Numerical Method 10
2.1.2 Capsules in an Unbounded Simple Shear Flow 14
2.1.3 Lateral Migration of Capsules in Shear Flow 17
2.1.4 Capsules in an Oscillatory Shear Flow 22
2.2 Behavior of Red Blood Cells 26
2.2.1 Mechanical Modeling of RBCs 26
2.2.2 An RBC in Simple Shear Flow; Tumbling-Swinging Transition 28
2.2.3 An RBC Flowing Thorough a Micropore 32
2.3 Cell Adhesion in Microvessels 34
2.3.1 Margination in Microvessels 35
2.3.2 Cell Adhesion in Capillaries 41
2.3.3 Malaria Infection 45
2.4 Formation and Destruction of the Primary Thrombus 50
2.4.1 Physiology and Pathology of Primary Thrombus
in Blood Flow 50
2.4.2 Particle Method Simulation 52
2.4.3 Simulation of Primary Thrombus Formation and Influence of
Vessel Geometry 54
2.4.4 Influence of Platelet Glycoprotein Receptors and SIPA 55
2.4.5 Interaction Between Platelets and RBCs on the Primary
Thrombus Formation and Mechanical Hemolysis 58
2.4.6 Summary 62
References 63
2.1
BEHAVIOR OF CAPSULES IN FLOW
Stephanie Nix
Department of Machine Intelligence and Systems Engineering, Akita Prefectural
University, Akita, Japan
A nyári éj.