Chapter 2
Materials of the Cell and Matrix
2.1 Basic Cellular Constituents
All cellular structures are made with same building blocks: atoms of (in descending
concentrations) carbon, oxygen, hydrogen, nitrogen and phosphorus, sulphur, and several
other atoms in minute quantities. These atomic building blocks are assembled into larger
blocks, i.e. amino acids & sugars, that are then strung together in even larger blocks, ie.
proteins and carbohydrates, schematically shown below:
Proteins
Figure 2.1 Assembly of
basic structural
components of the cell
Carbohydrates
Biomembranes
Amino Acids
Atoms
Carbon
Oxygen
Hydrogen
Nitrogen
Phosphorous,
Sulphur, etc.
Sugars
Phospholipids
Monomeric
Building Blocks
Polymeric
Structural
Components
Size and
Complexity
As you can see, our study of cell materials is greatly simplified by the fact that all
structural components are polymers strung together with 3 types of building blocks. The
structural components are mainly proteins, with some carbohydrates. The major
categories of cellular constituents are listed in Table 1 below:
Table 2.1 Chemical Components of Cells
Compound
Fraction in Cell
Relative Size of
(%)
molecule
Polarity of molecule
Water
70-80
Small
Polarized
Protein
(Polypeptide)
Lipid
(Fat)
Carbohydrate
(Sugars)
Salts
(Electrolytes)
10-20
Large
Regionally polarized
2-20
Medium
Non-Polarized
1-2
Medium to large
Regionally polarized
Small
Polarized
1
Note from the table that electrical polarity varies among the molecules. The importance
of these differences to cell mechanics will be appreciated in our study of Energetics in
Chapter 7. Note that lipids are non-polarized, however some amino acids are also nonpolarized. Carbohydrates can exist as simple sugars, of medium size, or as larger
complex chains, such as the backbone of DNA. 2
Besides polarity and size, other important properties of molecules are their solubility,
stability, and shape. As we shall see, proteins are the molecules whose shape is the most
varied, and most important determinant of their function.
In addition to the structural components, a second category of components is the
electrolytes, and monomeric molecules dissolved within the cell soup; these include the
major salts, and the building blocks: amino acids, sugars, and cell fuels such as ATP. The
major electrolytes consist of (in order of descending concentration in the cell): Cl-, K+,
Na++, Ca++, and Mg++. These salts are all surrounded by several water molecules, attached
by hydrogen bonds. 3
2.2 Arrangement of Cellular Materials
To help understand the material make-up of cells and matrix, it is entertaining to imagine
how they first sprung up in evolution, even though its details will never be known. The
following somewhat fanciful history is therefore to be pondered in that light. In the
beginning there was primordial soup: a rich sea filled with organic compounds. Over the
eons, as the chemicals began to aggregate in the slime, a critical mass of them was
captured within a volume surrounded by a barrier: a lipid membrane. Since oil and water
do not mix, a lipid bubble is the logical vessel for the aqueous contents of the cell to
reside. Thus a thin hydrophobic shell separated the hydrophilic from their surroundings.
With time this primitive cell, a prokaryote would have had to develop structures to
survive, since lipid bubbles are easily squashed. Hence the CSK was needed, and the rest
is history. Now lets take a look under the hood (Figure 2.2).
Figure 2.2 Peeling away the cell membrane
The first thing we notice is that the biomembrane is a lipid bilayer, arranged as an
amphiphile. This means that the molecular structure has both hydrophilic and lipophilic
parts, as shown in the schematic of a cross-section below.
H2Polar
O Phosphate Heads
Figure 2.4 Lipid Bilayer
H2O
70 A
H2O
Hydrophobic core
The Phosphate heads are negatively charged, so the outside layers of the phospho-lipid
sandwich quite happily dissolve in water. The core, composed of long hydrocarbon tails,
i.e. fatty acids, behaves oppositely, repelling water and all hydrophilic compounds. Thus
the bilayer is elegantly arranged to exist with both faces in water, allowing the middle to
act as a barrier to movement of water-based materials. Since the membrane separates the
cell plasma from the extra-cellular milieu, it is called the plasma membrane (PM).
While the PM can be considered part of the CSK, it is relatively weak. It does have
measurable stiffness, however, in shear, compression and bending, as will be seen in
Chapter 4. Being essentially a Newtonian fluid, the bilayer by itself has no tensile
strength. To illustrate, look at the picture sequence below, showing 2 vesicles whose
walls are pure lipid bilayers. Starting from the bottom picture, you see the vesicles just
touching. The next 2 pictures on top were made as the vesicle at right is pushed out by
pressure from the pipette holding it. Note that the vesicles pass into each other. This
ghost-like behaviour is due to their liquid nature.
3. Vesicles pass through
each other.
Figure 2.5
vesicle ghosts
2. Pipette pushes vesicle
out.
1. Vesicles make contact
An anecdote about the biomembrane is that the first estimate of its thickness is attributed
to Benjamin Franklin. The story goes that he poured a volume of cooking oil into a small
pond until it was entirely covered with oil. He then divided the volume of oil poured by
the area of the pond, finding the thickness was about 30 A. The close correspondence of
this number with present day measurements of lipid monolayers illustrates the power of
simple experiments. It also demonstrates the property of phospholipids to self-assemble
into a structure, i.e. a membrane.
2.3 CSK Components
Underneath the membrane, and penetrating it at many points, is the CSK. The first set of
components that is encountered contains different proteins each with separate functions,
as depicted in the schematic diagram below (Figure 2.6).
Figure 2.6 CSK
The extracellular matrix (ECM) consists of filamentous proteins, including collagen,
fibronectin, vimentin, titin and others. Note that the CSK connects with ECM via Integrin
molecules that consist of alpha and beta subunits. These subunits have ligands for
specific receptors on matrix proteins. Integrin thus crosses the plasma membrane (PM) to
serve as the connector. The standard active ligand of Integrin is the amino acid sequence,
RGD. Circulating cells such as white blood cells, and platelets use their Integrin as an
antenna to locate cells were their function is needed. The Figure below shows an Integrin
of a platelet. With its 2 subunits, integrin resemble both in form and function, a staple.
Several other cellular proteins bind with the ECM, as will be detailed in Chapter 11. 4
Figure 2.7 Integrin
The most abundant filament in most cells is filamentous actin (F-actin). This
microfilament is most prominent around cell perimeters, and serves as a rope tying the
network of other proteins together. Actin can also sustain some compression. A notable
exception to this cellular dependence on actin for rigidity is the red blood cell, whose
CSK is rich in Spectrin. Actin (specifically F-actin) is integral to contraction and motility
in most cells, Another type and configuration of actin is globular, or G-actin. Both types
exist in cells, as seen below, with the F-actin stained green, and G-actin stained orange
(different gray shades for this B/W rendering).
F- actin
G actin
Figure 2.8 Actin in a fibroblast
Many other proteins link the main filamentous actin to the membrane, including tensin,
talin, and - actinin, and vinculin, as shown in the cartoon. Although these many
proteins, including Integrin, are not abundant, they play crucial roles in mechanical
signalling, as we will see in subsequent chapters.
Recalling from Chapter 1, the CSK can be broken down into 3 major components:
microfilaments, intermediate filaments, and microtubules. Single strand diameter of these
proteins ranges from about 10 nM for microfilaments, 15 nM for intermediate filaments,
and 20 nM for microtubules. Filaments usually form multi-stranded threads, so large
bundles of microfilaments are common. Microtubules (MT) are seen in abundance in the
cells below, differently shaded from actin. Note that MTs tend to be straighter and run
closer to the nuclei, although they extend to cell perimeters as well. MTs are hollow
tubes, whereas the other 2 filaments are ropes and rods (See Figure 1.7).
MT
Actin
Figure 2.9
The CSK is thus structured as a porous network of struts. This plan is, in fact, no different
than that of all living materials: even bone, the densest material in the body, is composed
of geodesic structures at the meso-scale. The millimeter-size sub –units are arranged in a
lattice oriented to maximize strength in the direction of principal stress. Bone, like the
CSK is a strong, shock absorbing material that distributes mechanical energy to the
network, but tends to focus large, chronic stresses to stronger and thicker support
elements.
It should be noted that CSK composition varies from cell to cell, and even region to
region within one cell depending on function as well as developmental state. For
example, red cells are rich in spectrin, but deficient in actin. Muscle cells, in contrast,
have a very high actin content. Growing or healing cells may have relatively high actin in
their growing portions. Some cells, such as skin cells of young humans or certain animals
(see below) are rich in elastin.
Chemistry of CSK Proteins
TO understand the assembly and maintenance of the CSK it is necessary to examine
some details of the chemistry of the major proteins. This can be done by dissociating the
3 major proteins from cells, and re-assembling them separately in vitro to study their
behaviour. These studies have found some features that are common to all 3, and some
that are peculiar to only one. For example, all CSK proteins assemble from monomers,
they are all helical, and hence possess multiple equivalent binding sites, they form
diverse structures based on statistical mechanics rather than strictly deterministic
pathways, and all are polar, that is they each have a chemically distinct head and tail.
Actin starts out its existence as a single monomeric protein that is translated from its
gene.
2.4 Cytogel
The cytosol is a gel containing electrolytes, amino acids, carbohydrates, metabolic fuels
and products, as well as cellular organelles, such as mitochondria and endoplasmic
reticulum, and others depending on cell type. The cytoplasm, since it is a gel, contibutes
some mechanical stiffness properties to the cell. Ca++ plays a major role in maintaining
the ‘cytogel’ since it coordinates polymer-polymer interactions. The cytogel is formed
when the negatively charged polymers in the cytosol (proteins and nucleotides) are
trapped together, creating osmotic pressure for water influx. A schematic of a gel is
shown in Figure 1.8 below.
Figure 2.10
Gel
Gel
H20
Factors
Ca++, pH
Swelling pressure = osmotic pressure- elastic (compressive)
pressure
Polymer-polymer
Intra-polymer
osmosis
Focal adhesion complexes (FACs) are mechanical linkages signal relay stations between the
[1]
cytoskeleton and ECM Usually attached to the FACs, stress fibers are bundles of actin
filaments with myosin; they are components of the cytoskeleton and generate contractile
forces during cell crawling, thus serving as a mechanical actuator.
2. 9 Exercises
1. Analogy has been made between integrin and a staple. Explain how this might apply.
2. Draw a monovalent electrolyte in the hydrated state, using ball and sticks to represent
molecules. You need not be quantitatively accurate about the hydration state. How
would this compare with a divalent electrolyte?
3. What does polarity have to do with solubility? Give an example.
4. What cellular components serve as ropes or rods?
5. Describe what mechanical role the cytogel might serve. Make a Simulink model of it.
6. Which of the following statements are correct? Explain
your answers.
A. Proteins are so remarkably diverse because
each is made from a unique mixture of amino
acids that are linked in random order.
B. Lipid bilayers are macromolecules that are
made up mostly of phospholipid subunits.
C. Nucleic acids contain sugar groups.
D. Many amino acids have hydrophobic side
chains.
E. The hydrophobic tails of phospholipid molecules
are repelled from water.
F. DNA contains the four different bases A, G, U,
and C.
2.
http://www.bio.unc.edu/courses/2004spring/biol052-006/ch02final.pdf
3.
http://www.science.uwaterloo.ca/~cchieh/cact/applychem/waterbio.html
4.
Vuori, K., Integrin signaling: Tyrosine phosphorylation events in focal adhesions. Journal of
Membrane Biology, 1998. 26(3): p. 191-199.