7 1.

1 A brief history of biomechanics

 
  Figure 1.2
  Figure from Borelli’s classic work, De Motu Animalium (On the Movement of Animals). Panels 1–4 show how elastic
  bands (representing muscles) can interact with two pivoting levers (representing bones) in a variety of geometric
configurations. Panels 5 and 6 demonstrate how the muscle and bone configurations act in humans carrying loads.
  Panels 7 and 8 show various pulley arrangements, while panels 9 and 10 show how muscle action in the human arm
  supports a weight R. (We will revisit this subject in Ch. 8.) The concepts may not seem advanced to modern students,
  but to put things into context, it should be remembered that the first volume of De Motu Animalium was published seven
years before the appearance of Newton’s Principia.
 
 
 
 
 
 
 
 
 5 1.1 A brief history of biomechanics

Figure 1.1
Portraits of Drs. William Harvey (left) and Stephen Hales (right). Both were early biomechanicians; Harvey was a noted
English physician, while Hales was a Reverend and “amateur” scientist. Both portraits, courtesy of the Clendening
History of Medicine Library and Museum, University of Kansas Medical Center [18].  
 
  in the cardiovascular system. For example, he carried out careful dissections and
  correctly noted that all the valves in veins acted to prevent flow away from the
    suggesting that the function of the veins was to return blood to the
heart, strongly
heart. For our purposes, his most intriguing argument was based on a simple mass
balance: Harvey reasoned that the volumetric flow of blood was far too large to be
supplied by ingestion of food. How did he do this? Using a sheep’s heart, he first
estimated the volume of blood pumped per heart beat (the stroke volume) as two
ounces of blood. Knowing the heart rate, he then computed that the heart must be
pumping more than 8600 ounces of blood per hour, which far exceeds the mass of
food any sheep would be expected to eat! In his words (italics added) [19]:

Since all things, both argument and ocular demonstration, show that the blood passes
through the lungs and heart by the force of the ventricles, and is sent for distribution to all
parts of the body, where it makes its way into the veins and porosities of the flesh, and then
flows by the veins from the circumference on every side to the center, from the lesser to the
 9 1.1 A brief history of biomechanics

Figure 1.3
Portraits of Drs. Jean Poiseuille (left) and Thomas Young (right). Both men did important work in physiology and
medicine, yet are familiar to engineering students: Poiseuille for his work on steady laminar incompressible flow in a
tube of uniform circular cross-section (Hagen–Poiseuille flow) and Young from his work on the elasticity of bodies
(Young’s modulus of elasticity). Poiseuille portrait reproduced with permission from [24] as modified by Sutera [25];
Young portrait by Sir Thomas Lawrence, engraved by G. R. Ward, as shown in Wood [26].
 
   
eye, and deduced that the focussing power of the eye resulted from changes in the
shape of the lens. He devised a device for measuring the size of a red blood cell, with
his measurements showing a size of 7.2 µm [26], a value that is remarkably accurate
(see Ch. 3). He also studied fluid flow in pipes and bends, and the propagation of
impulses in elastic vessels, and then applied this to analysis of blood flow in the
arteries. He correctly deduced that peristaltic motion of the artery wall did not
contribute to the circulation of blood, and instead that the motive power must
come from the heart [31]. He is most familiar to engineering students for defining
the modulus of elasticity, now known as Young’s modulus in his honor.
Julius Wolff (1836–1902) and Wilhelm Roux (1850–1924) were German physi-
cians (Fig. 1.4). Of the two, Wolff is better known to biomedical engineers because
 10 Introduction

Figure 1.4
Portraits of Drs. Julius Wolff (left) and Wilhelm Roux (right). Both were German physicians who were interested in how
mechanical forces could influence the structure and development of bone. Both portraits, courtesy of the Clendening
History of Medicine Library and Museum, University of Kansas Medical Center [18].
 
   
of his formulation of “Wolff’s law” of bone remodeling. Legend has it [32] that the
structural engineer Karl Culmann saw a presentation by the anatomist Hermann
von Meyer, in which von Meyer described the internal architecture of the bone in
the head of the femur. Culmann was struck by the similarity between the pattern
of solid elements in the cancellous (“spongy”) bone of the femur and the stress
trajectories5 in a similarly shaped crane that he was designing (Fig. 1.5).6 Based
on von Meyer’s paper describing this similarity [33], as well as other data avail-
able at the time, Wolff hypothesized that bone was optimized to provide maximum
strength for a minimum mass. He then went on to formulate his “law” of bone

5
A stress trajectory is an imaginary line drawn on a surface that is everywhere tangent to the principal stress directions on
the surface. Stress trajectories help to visualize how the stress is carried by an object, and they can be used as the basis
of a graphical procedure for determining stress distributions in bodies. This graphical solution method is now obsolete,
having been replaced by computational methods.
6
This certainly emphasizes the importance of interdisciplinary interaction in biomedical engineering!
 11 1.1 A brief history of biomechanics

Figure 1.5
Comparison of internal architecture of cancellous bone in the head of a femur (large drawing at right) and the stress
trajectories in the head of a crane (large drawing at left). The smaller drawings provide details of the mechanics of the
crane and the stress distributions in various structures. This picture originally appeared in the article by von Meyer [33],
as reproduced in [32].
 
   
remodeling [34,35]:7 “Every change in the form and the function of a bone or of
their function alone is followed by certain definite changes in their internal archi-
tecture, and equally definite secondary alterations in their external confirmation,
in accordance with mathematical laws.” In simpler terms, Wolff stated that bone
will adapt its internal architecture in response to external constraints and loads.
Wolff went on to claim a rigorous similarity between cancellous bone architecture
and stress trajectories. Cowin has shown that this is based on a false comparison of
apples and oranges (i.e., a continuous material vs. a porous one) [32] and argued
persuasively that Wolff gets rather too much credit for his remodeling law, possi-
bly because he was a more prolific writer on this topic. Cowin [32] suggested that
the anatomist Roux should get at least as much credit as Wolff for this “law” of

7
Wolff’s original book was in German [34], but an English translation exists [35].
 20 Cellular biomechanics

Microfilaments
Plasma membrane

Secretory vesicle

Microtubule
Lysosome

Centrioles
Peroxisome

Golgi apparatus Mitochondrion

Free ribosome

Nucleus
Bound ribosome
Nucleolus
Granular
endoplasmic
reticulum Nuclear envelope

Nuclear pore

Agranular
endoplasmic
reticulum

 
  Figure 2.1
 
Structures and organelles found in most human cells. This diagram is highly schematized but serves to indicate the
major features of the cellular organelles. From Vander et al. [3]. Reproduced with kind permission of the McGraw-Hill
Companies.

When engineers talk about the mechanics of conventional engineering materials,

they can refer to handbooks that tabulate the properties of, for example, different
types of stainless steel, and describe the internal structure of these steels. Can
we do that for cells? Not quite, but a body of data is slowly being accumulated
about the “mechanical properties of cells.” In Section 2.5, we will tackle the tricky
question of how one measures the mechanical properties of a single cell, while in
Section 2.6 we will introduce some engineering models that, in combination with
experimental data, teach us something about the cell’s internal mechanics.
 lar organelles can use. This common molecule is adenosine triphosphate
ormed from adenosine diphosphate (ADP) and phosphate (PO2− 3 ) in the
ng reaction:

24 ADP + PO2− + energy + 2H+ → ATP

Cellular biomechanics 3
 
2−
s stored in the chemical bond between Primary LoopADP and PO
3 (Fig. 2.3). A mechan-
Secondary Loop

ogue is a spring, which Fuel + starts in Wateran +uncompressed

steam To
state (ADP) and is then
turbines
oxygen
2−
ssed and held in place by Burner a catch
+
(PO 3 ). The organelles can “release the
Secondary Heat
o produce energy, with by-products Primary Heat
Exchanger ADP and PO2−
Exchanger
3 . We say, therefore, that
he common currency CO +
of energy within the cell. Return
from
2 turbines
mportant to note that ADP and phosphate are recycled, to be once more
H O 2
Water

ed in the mitochondria to yield Energy ATP. Flow

This is similar to the movement of
loop cooling water
protein, fats +in a thermal generating station,
Carbohydrates,
ATP and it emphasizes that
Organelle
products
oxygen
merely a transient carrier of energy within the cell (Fig. 2.4).
Mitochondria Organelles

CO2 + Raw
H2O ADP + PO32− materials

Figure 2.4
Energy flow in a thermal generating station (top) and a cell (bottom). Note that primary loop cooling water is analogous
to ATP in that it is a transient vehicle for energy storage which is recycled.  
   
! provides mechanical strength and integrity to the cell
! is central to the intracellular transport of organelles, especially in large cells

! is essential during cell division, where it plays a key role in many processes,
such as axons

including chromosome separation in mitosis and meiosis.

The cytoskeleton consists of three types of filament, each with a specialized pro-
tein composition: actin filaments (7–9 nm in diameter), intermediate filaments
(10 nm in diameter), and microtubules (approximately 24 nm in diameter). Actin
filaments are also called microfilaments or – in skeletal muscle cells – thin fila-
ments. The interaction between all three filament types helps to determine the cell’s
mechanical behavior. We will briefly review the function of each of these filament
types.
 35 2.5 Measurement of mechanical properties

Table 2.2. Typical magnitudes of quantities measured on the cellular scale

(last column)

Quantity SI units “Micro SI” units (suitable for cells)

Distance m µm
a
Force N pN (= 10−12 N) to nN (= 10−9 N)
Pressure, Pa (= N/m2 ) pN/µm2 (= 1 Pa) to nN/µm2 (= 1 kPa)
stress
36 Cellular biomechanics  
  a
Forces of molecular bonds and those exerted by “soft” cells are in the picoNewton range. “Stiff” cells
can
A exert forces in the nanoNewton range.
B
Cantilever
Surface force
fibrous matrix outside the cell. We will consider the important role integrins play in
apparatus
cellular biomechanics and the sensing10 of mechanical
nN–1 µN signals later in this chapter.
AFM
0.01 nN–100 nN
2.5 Methods to measure the mechanical properties
of cells and biomolecules
Spring

To help in understanding cellular biomechanics we need experimental data on

the mechanical properties of individual cells, such as Young’s modulus, shear
modulus, etc. It is also useful to have measurements of the mechanical strength of
C
individual molecules (e.g., actin filaments) and of bonds between molecules, e.g.
Micropipette aspiration
between a receptor and its ligand.
0.01–1000 nNHow does one measure Young’s modulus for a
cell or a molecule? As you may imagine, it is not trivial. Consider, for instance, the
magnitudes we are dealing with at the cellular level. These are discussed very nicely
byDHochmuth in a review article [28] and are summarized in Table 2.2. It can be
Optical tweezers
seen that the forces
0–200 pNare pretty small! Nonetheless, there are a number of techniques
for measuring the mechanical properties of single cells and molecules. Some of
these techniques are summarized schematically in Fig. 2.16. Each technique is
suited to a different force range and length scale. Below we review some of them.
Figure 2.16

2.5.1 Atomic force microscopy

Schematic diagrams of force probes used to measure the mechanical properties of single cells and protein interaction
forces. (A) An atomic force microscope (AFM) shows the probe tip, attached to the cantilever force transducer, coming in
contact with a substrate. (B) A surface force apparatus, showing the crossed cylinders of the apparatus and the
force-transducing spring. (C) The bioforce probe, consisting of a cell partially aspirated into a micropipette. A bead
The atomic force microscope (AFM) is a powerful tool for measurement of forces
(center black sphere) is attached to one cell (left), and a force between the bead and a second cell or glass bead (right)
and displacements
is exerted by aspirating the (left) on both
cell into molecular
the pipette. and Acellular
(D) Optical tweezers. bead is held inscales
the optical[30,31].
trap, such that The key ele-
radiation pressure exerted on the bead applies force to adhesive contacts between materials on the bead surface and the
ment of the microscope is a tapered probe, typically made from silicon or silicon
substrate. Modified with permission from Leckband [29].
nitride, which is attached to a cantilever arm. When the probe tip interacts   with
apiezoelectric
sample, the arm is
element thatdeflected.
can move inThis deflection
the vertical can be measured
and transverse by sensing the
(lateral) direc-
position
tions. In of a laser applications,
biological beam that reflects
the AFMoff the cantilever
is typically used inarm (Fig. 2.17).
conjunction with By suitable
an optical microscope
placement that and
of the laser can bedetector
used for real-time visualization,of
to take advantage forthe
example, to level arm”
“optical
help to localize the AFM probe over a target cell. One of the great advantages
effect, displacements of less than 1 nm can be measured. The arm is attached to a of
the AFM is that imaging can be carried out on living cells or intact molecules in
an aqueous environment. This is in contrast to other high-resolution microscopy
techniques (e.g., scanning electron microscopy) that require that the samples be
fixed and imaged in a near-vacuum.