Cell & Molecular
Cell & Molecular
Felix Osei-Boakye
Ph.D Haematology & Transfusion Science (in-view),
MPhil. Haematology, BSc, & Dip. (Med. Lab. Science).
Sunyani Technical University
Department of Medical Laboratory Science
1
THE CELL
2
THE CELL
• Every animal or plant is a vast colony of individual cells, each of which performs a
specialized function that is integrated by intricate systems of cell-to-cell
communication
3
The Cell
• Some require oxygen to live, whereas, for others the gas is deadly
- Some cells consume little/more carbon dioxide (CO2), sunlight, and water as their
raw materials
- Also, others need a complex mixture of molecules produced by other cells
• *
4
The Cell
• Despite the extraordinary diversity of plants and animal species, people have
recognized from time immemorial that these organisms have something in
common that entitles them to be called living organisms
- Sensitive or respond to the environment, capable of reproduction, growth and
development, regulation, homeostasis, and energy processing
• Another property of living cells is the presence of soluble enzymes located in the
cytoplasm
- Cellular enzymes catalyze biosynthesis of the low molecular weight precursors to
protein and nucleic acids
5
The Cell
6
Prokaryotic Cell
• Prokaryotes include cells of two domains, the Archaea and the Bacteria, which
diverged early in evolution
- The Archaea include cells that live in extreme environments that are unusual today
but may have been prevalent in primitive Earth. For example, thermoacidophiles live
in hot sulfur springs with temperatures as high as 80°C and pH values as low as 2
• All prokaryote cell components are located together in the same compartment
- They are made of a single compartment
• Prokaryotic cells are smaller and simpler than most eukaryotic cells, their
genomes are less complex, and they do not contain nuclei
8
Prokaryotic Cell
• The largest and most complex prokaryotes are the Cyanobacteria - bacteria in
which photosynthesis evolved
9
Photograph of a primitive hot spring in East Africa
Hot springs are good sites to find archaea
10
Eukaryotic Cell
11
Eukaryotic Cell
• Like prokaryotic cells, all eukaryotic cells are surrounded by a plasma membrane
and contain ribosomes
• However, eukaryotic cells are much more complex and contain a nucleus and a
variety of cytoplasmic organelles
• The largest and most prominent organelle of eukaryotic cells is the nucleus, with
a diameter of approximately 5μm
• The nucleus contains the genetic information of the cell, which in eukaryotes is
organized as linear rather than circular DNA molecules
• The nucleus is the site of DNA replication and of RNA synthesis; the translation of
RNA into proteins takes place on ribosomes in the cytoplasm
12
Eukaryotic Cell
• Eukaryotic cells are generally much larger than prokaryotic cells, frequently
having a cell volume at least a thousandfold greater
• The larger and more complicated cells of higher eukaryotic organisms (animals,
fungi, plants, and protists) are subdivided into separate compartments and are
called eukaryotic cells.
13
Features that Distinguish Eukaryotic and Prokaryotic Cells
Assignment 1
14
Cellular Organization
- Cells of skeletal muscle, liver, and other tissues may have up to 50 nuclei and are
multinucleate
15
The Plasma Membrane
• Our cells are surrounded by an outer membrane (plasma membrane) that is formed
by phospholipid and protein
• The plasma membrane separates the inside of the cell (cytoplasm) from the
outside
- Therefore, it serves as an interface that allows the internal part of the cell to interact with
the external environment
• The membrane is physically weak and flexible. Most bacterial and plant cells have
hard cell walls, though animal cells usually do not
• The plasma membrane is a phospholipid bilayer with proteins either attached (also
called peripheral proteins) or embedded (also called integral proteins)
16
The Plasma Membrane
17
Cellular Organization
The Plasma Membrane
18
The Plasma Membrane
• Short chains of sugars are attached to the outer surfaces of some protein and
lipid molecules (called glycoproteins and glycolipids, respectively)
- These carbohydrate chains, specific to each cell, mark the cell as belonging to a
particular individual
- Such cell markers account for such characteristics as blood type or why a patient’s
system sometimes rejects an organ transplant
20
Cellular Organization
The Nucleus
• The presence of a nucleus is the principal feature that distinguishes eukaryotic cells
from prokaryotic cells
• DNA replication, transcription, and RNA processing all take place within the
nucleus, whereas, the final stage of gene expression (translation) localized to the
cytoplasm
21
Cellular Organization
The Nucleus
• The unique chemical composition of each person’s DNA forms the basis for DNA
fingerprinting
• The nucleus is separated from the cytoplasm by a double membrane known as the
nuclear envelope, which is continuous with the endoplasmic reticulum
• The nuclear envelope has nuclear pores of sufficient size to permit the passage of
proteins into the nucleus and ribosomal subunits out of the nucleus
• Additionally, the double membrane of the nuclear envelope surrounds and contains
cellular DNA, protecting the vital genetic information contained within its molecules
22
Cellular Organization
Ribosomes
• Ribosomes are composed of two subunits, one large and one small. Each subunit
has its own mix of proteins and rRNA
• Protein synthesis occurs at the ribosomes
• Ribosomes are found free within the cytoplasm either singly or in groups called
polyribosomes (called polysomes for short)
• Ribosomes are often attached to the endoplasmic reticulum, a membranous
system of saccules and channels
• Proteins synthesized by cytoplasmic ribosomes are used inside the cell for various
purposes. Those produced by ribosomes attached to endoplasmic reticulum may
eventually be secreted from the cell
23
Cellular Organization
Endoplasmic Reticulum
• The endoplasmic reticulum (ER), a complicated system of membranous channels
and saccules (flattened vesicles), is physically continuous with the outer
membrane of the nuclear envelope. Rough ER is studded with ribosomes on the
side of the membrane that faces the cytoplasm
• Here proteins are synthesized and enter the ER interior where processing and
modification begin. Some of these proteins are incorporated into membrane, and
some are for export. Smooth ER, which is continuous with rough ER, does not have
attached ribosomes
• Smooth ER synthesizes the phospholipids that occur in membranes and has
various other functions, depending on the particular cell
- In the testes, it produces testosterone, and in the liver it helps detoxify drugs
24
Cellular Organization
Mitochondria
• Are bounded by a double membrane
• The inner membrane is folded to form little shelves called cristae, which project
into the matrix, an inner space filled with a gel-like fluid
• Mitochondria are the site of ATP (adenosine triphosphate) production involving
complex metabolic pathways
- ATP molecules are the common carriers of energy in cells
• *
25
Cellular Organization
Mitochondria
• The mitochondrion is often called the powerhouse of the cell
• Just as a powerhouse burns fuel to produce electricity, the mitochondria convert the
chemical energy of carbohydrate molecules into the chemical energy of ATP
molecules
• In the process, mitochondria use up oxygen and give off carbon dioxide and water
• The oxygen you breathe in enters cells and then mitochondria; the carbon dioxide
you breathe out is released by mitochondria
- Because oxygen is used up and carbon dioxide is released, we say that mitochondria
carry on cellular respiration
26
Cellular Organization
Mitochondria
• Fragments of digested carbohydrate, protein, and lipid enter the mitochondrial
matrix from the cytoplasm
• The matrix contains enzymes for metabolizing these fragments to carbon dioxide
and water
• Energy released from metabolism is used for ATP production, which occurs at the
cristae
- The protein complexes that aid in the conversion of energy are located in an assembly-
line fashion on these membranous shelves
• Many cells use ATP to carry out their specialized functions
- For example, muscle cells use ATP for muscle contraction, which produces movement,
and
- nerve cells use it for the conduction of nerve impulses, which make us aware of our
environment
27
Cellular Organization
The Cytoskeleton
• Several types of filamentous protein structures form a cytoskeleton, and this helps
to maintain the shape of the cell, and either anchors the organelles or assists
their movement as appropriate
• The cytoskeleton includes microtubules, intermediate filaments, and actin filaments
28
Cellular Organization
The Cytoskeleton
b. Intermediate filaments differ in structure and function. Because they are tough
and resist stress, intermediate filaments often form cell-to-cell junctions
• Intermediate filaments join skin cells in the outermost skin layer, the epidermis
c. Actin filaments are long, and extremely thin fibers that usually occur in bundles
or groups
• Actin filaments have been isolated from various types of cells, especially those in
which movement occurs
• Microvilli, which project from certain cells and can shorten and extend, contain actin filaments.
Actin filaments, like microtubules, can assemble and disassemble
29
DISCUSSION
30
TRANSPORT ACROSS THE PLASMA MEMBRANE
31
Transport across the plasma membrane
Simple Diffusion
• Diffusion is the spontaneous movement of simple atoms or molecules from an
area of higher concentration to an area of lower concentration until they are
equally distributed
• Eventually eliminating the concentration difference between the two regions
- To illustrate diffusion, imagine putting a tablet of dye into water
- The water eventually takes on the color of the dye as the dye molecules diffuse
32
Transport across the plasma membrane
Simple Diffusion
• The chemical and physical properties of the plasma membrane allow only a few
types of molecules to enter and exit a cell by simple diffusion
- However, lipid-soluble molecules such as alcohols can diffuse through the membrane
because lipids are the membrane’s main structural components
• Gases can also diffuse through the lipid bilayer; this is the mechanism by which
oxygen enters cells and carbon dioxide exits cells
- For example, consider the movement of oxygen from the lungs to the bloodstream
- When you inhale, oxygen fills the tiny air sacs (alveoli) within your lungs. Neighboring
lung capillaries contain red blood cells with a very low oxygen concentration
- Oxygen diffuses from the area of higher (oxygen) concentration to the area of lower
(oxygen) concentration: first through alveolar cells, then lung capillary cells, and
finally into the red blood cells
33
Transport across the plasma membrane
Simple Diffusion
• When atoms or molecules diffuse from areas of higher to lower concentration
across plasma membranes, no cellular energy is involved
• Instead, kinetic or thermal energy of matter is the energy source for diffusion
34
Transport across the plasma membrane
Osmosis
• In osmosis, there is the movement of solvent molecules across a
semipermeable membrane, from a region of higher water concentration to a
region of lower water concentration
• Water molecules move more rapidly through the membrane of a cell than
dissolved ions or small polar organic solutes, which are considered
nonpenetrating
- Because of this difference in the penetrability of water versus solutes through the
plasma membrane, the membrane is said to be semipermeable
35
Transport across the plasma membrane
Osmosis
• Osmosis occurs whenever an unequal concentration of water exists on either
side of a selectively permeable membrane
- In a solution, water is more concentrated when it contains fewer dissolved
substances, or solutes, (and thus is closest to pure water)
- Water is less concentrated as solute concentration increases
• (Recall that a selectively permeable membrane allows water to pass freely, but
not most dissolved substances)
36
Transport across the plasma membrane
Osmosis
37
Transport across the plasma membrane
Osmosis
38
Transport across the plasma membrane
Osmosis
(a) A cell placed in a
hypotonic solution (one
having a lower solute
concentration than the cell)
swells because of a net gain
of water by osmosis
Facilitated Transport
• Substances always diffuse across the plasma membrane, when the concentrations
of substances on either sides/regions of the membrane are different
• However, most solutes do not simply diffuse across a plasma membrane
- Also, they do not always diffuse through the lipid bilayer or through a channel
- Instead, they are transported by means of protein carriers within the membrane
• The cell does not require energy for this type of transport because the molecules
are moving down their concentration gradient
40
Transport by Carriers
Facilitated Transport
• Facilitated diffusion mediates the entry and exit of polar solutes, such as sugars
and amino acids, that do not penetrate the lipid bilayer
• Unlike ion channels, which can conduct millions of ions per second, most
facilitative transporters can move only hundreds to thousands of solute molecules
per second across the membrane
• The activity of facilitative transporters can be regulated, like enzymes and ion
channels
41
Transport by Carriers
Facilitated Transport
• In many cases, the diffusing substance
first binds selectively to a membrane-
spanning protein, called a facilitative
transporter, that facilitates the
transport/diffusion process
42
Transport by Carriers
Active Transport
• This is an energy-driven process where membrane proteins transport molecules
or ions across a cell membrane from a region of lower concentration to a region of
higher concentration, against the concentration gradient
• Active transport requires a protein carrier and the use of cellular energy obtained
from the breakdown of ATP
- There is one type of pump that is active in all cells but is especially associated with
nerve and muscle cells
- This pump moves sodium ions (Na+) to the outside of the cell and potassium ions (K+) to
the inside of the cell
*
43
Transport across the plasma membrane
Active Transport
• When ATP is broken down, energy is released, and in this case the energy is
used by a carrier to carry out active transport
• Therefore, cells involved in active transport have a large number of mitochondria
near the plasma membrane at which active transport is occurring
44
DISCUSSION
45
Transport across the plasma membrane
• Eukaryotic cells are also able to ingest large particles (such as bacteria) and
the uptake of fluids or macromolecules in small vesicles from the surrounding
medium by a distinct process called endocytosis
46
Transport across the plasma membrane
• During exocytosis, a vesicle fuses with the plasma membrane as secretion occurs
47
Transport across the plasma membrane
48
THE CELL CYCLE
Felix Osei-Boakye
Ph.D Haematology & Transfusion Science (in-view),
MPhil. Haematology, BSc, & Dip. (Med. Lab. Science).
Sunyani Technical University
Department of Medical Laboratory Science
49
THE CELL CYCLE
• A cell reproduces by carrying out an orderly sequence of events in which it
duplicates its contents and then divides in two
• This sequence of events from the time a cell divides to the time the resulting daughter cells
also divide is called “the cell cycle”
• The cell cycle in higher eukaryotes is carefully regulated by internal and external
signals
- For example, growth factors are external signals received at the plasma membrane
that cause a resting cell to undergo the cell cycle
- When blood platelets release a growth factor, skin fibroblasts in the vicinity finish the
cell cycle, thereby repairing an injury
• Other signals ensure that the stages follow one another in the normal sequence
and that each stage is properly completed before the next stage begins
50
The Cell Cycle
To explain how cells reproduce, it is important that we are able to answer these 3
major questions
1. How do cells duplicate their contents - including the chromosomes, which carry
the genetic information?
3. How do they coordinate all the steps and machinery required for these two
processes?
51
The Cell Cycle
• When appropriate signals are present, a cell doubles its organelles and
accumulates materials needed for DNA synthesis and cell division
• During the cell cycle, there is replication of genetic materials, subsequent mitosis,
and specialization of cells due to existing needs. These processes allow humans to
grow and also repair damaged tissues
• Although, the cell cycle focuses on cell proliferation, many cells in “animals” remain
permanently in a state of quiescence (G0 phase),
- whereas others can resume proliferation if stimulated by appropriate growth factors or
other extracellular signals
52
The Cell Cycle
Types of Cells
Proliferative (Labile) cells - these type of cells are constantly going through the
cell cycle
Examples of proliferative cells include:
• Epithelium of skin, Gastrointestinal tract (GIT), Urinary tract, Haematopoietic stem
cells (in the red bone marrow)
53
The Cell Cycle
Types of Cells
Stable cells – cells that do not replicate/go through the cell cycle all the time. These
type of cells can initiate the cell cycle when they are stimulated by a strong signal
• Liver cell (hepatocyte), Epithelium of kidney tubules, Alveolar cells of the lungs
Permanent cells (Amitotic) – once these types of cells have completed the cell cycle,
they do not go through it again
1. Interphase
− G1 Phase
− Synthesis Phase (S Phase)
− G2 Phase
2. Mitotic phase
− Mitosis
− Cytokinesis
• The passage of animal cells through the cell cycle is regulated primarily by the
extracellular growth factors that signal cell proliferation
• In the presence of the appropriate growth factors, a cell passes the restriction
checkpoint and enters the S phase 55
The Cell Cycle
• Once it has passed through the restriction point, the cell is committed to proceed
through the S phase and the rest of the cell cycle, even in the absence of further
growth factor stimulation
• However, if appropriate growth factors are not available in the G1, progression
through the cell cycle stops at the restriction checkpoint
• The arrested cell then enters a quiescent phase of the cell cycle called G0 phase,
where they can remain dormant for long periods of time without proliferating
56
INTERPHASE
• Two significant events occur during the interphase: these are replication of DNA
and protein synthesis
1. G1 Phase
• The cell doubles its organelles (mitochondria, ribosomes, etc) and accumulates
materials that will be used in DNA synthesis
- Some of which are proteins, including enzymes (like the replisomes)
• The proliferation of most animal cells is regulated in the G1 phase of the cell cycle
57
Interphase
58
Interphase
− Cell cycle checkpoints
• Progression through the cell cycle is stimulated by
extracellular signals, such as nutrients and growth
factors
• All events occurring in different stages of the cell cycle
must be coordinated with one another so that they occur
in the appropriate order
Apoptosis
• Any cell that did not successfully complete mitosis and is abnormal undergoes
apoptosis at the restriction checkpoint
• Apoptosis is often defined as programmed cell death because the cell progresses
through a series of events that bring about its destruction
- The cell rounds up and loses contact with its neighbors
- The nucleus fragments and the plasma membrane develops blisters
- Finally, the cell fragments and its bits and pieces are engulfed by white blood cells
and/or neighboring cells
3. G2 Phase
• This phase is primarily focused on cell growth. For example, the cytoplasm of the
cell increases in size in order to make provision for cell division
• The cell synthesizes proteins that will assist cell division, such as the proteins
found in microtubules
61
Summary
62
Discussion
63
MITOTIC PHASE
• After the interphase, the cell enters the M phase where cell division occurs
• There is division of the nucleus (Mitosis) and division of the cytoplasm
(Cytokinesis)
• During mitosis, chromosomes are distributed to two separate nuclei. When
cytokinesis is complete, two daughter cells are present
64
Mitotic Phase
Prophase
• Four major activities occur at this phase that indicate the cell is about to divide
• The two pairs of centrioles outside the nucleus begin moving away from each other
toward opposite ends of the nucleus
• Spindle fibers appear between the separating centriole pairs
• The nuclear envelope begins to fragment, and the nucleolus begins to disappear
• Condensation of the chromatin to sister chromatids
65
Metaphase
• The nuclear envelope is fragmented, and the spindle occupies the region formerly
occupied by the nucleus
• Spindle fibers attach to the centromeres as the chromosomes continue to shorten
and thicken
• The paired chromosomes are now at the equator (center) of the spindle. Metaphase
is characterized by a fully formed spindle, and each chromosome with two sister
chromatids, are aligned at the equator
66
Mitotic Phase
Anaphase
• The sister chromatids separate from each other. Once the chromatids are separated,
they are called chromosomes
• Separation of the sister chromatids ensures that each cell receives a copy of each
type of chromosome and a full complement of genes
• During anaphase, the daughter chromosomes move to the poles of the spindle
• Anaphase is characterized by the movement of chromosomes toward each pole and
thus, to opposite sides of the cell
67
Mitotic Phase
Telophase
• Telophase begins when the chromosomes arrive at the poles. During telophase, the
chromosomes become indistinct chromatin again
• The spindle disappears as nucleoli appear, and nuclear envelope components
reassemble in each cell. Telophase is characterized by the presence of two daughter
nuclei
68
Mitotic Phase
Cytokinesis
• Cytokinesis is division of the cytoplasm and organelles
• In human cells, a slight indentation called a cleavage furrow passes around the
circumference of the cell. Actin filaments form a contractile ring, and as the ring gets
smaller and smaller, the cleavage furrow pinches the cell in half. As a result each cell
becomes enclosed by its own plasma membrane
69
Summary of Mitosis
70
BIOLOGICAL RELEVANCE OF THE CELL CYCLE
Tissue repair/ tissue replacement
• Skin fibroblasts are arrested in G0 phase until they are stimulated to divide
- This becomes necessary when repair of damaged tissue resulting from a wound is
required
• This triggers the release of platelet-derived growth factor (PDGF) from blood
platelets during the clotting process
- This signal induces fibroblasts in the vicinity of the damaged tissue undergo the cell cycle
and proliferate in order to repair the damaged tissue
71
Biological relevance of the cell cycle
Conception and foetal development
• When appropriate signals are present, a cell doubles its organelles and accumulates
materials needed for DNA synthesis and cell division
- During the cell cycle, there is replication of genetic materials, and subsequent
mitosis
• These processes allow humans to grow by ensuring that a cell duplicates to produce
daughter cells of the same kind, and with the same number of diploid chromosomes
- During fertilization, a foetus inherits its genome from both parent gamete cells
(haploid cells) in order to possess a complete human genome, which typically
has 46 chromosomes: 23 each from maternal- and paternal sources
• As the foetus develops, mitotic division of the cells occurs in the mother’s uterus to
produce identical cells, and this enable the formation of tissues, organs/organ systems, and
the overall growth and development of the foetus
72
Monosomy 9
Several genes that control cell growth
and division are found on Chromosome 9
73
Trisomy 21
Causes Down Syndrome
Characterised by developmental and intellectual delay
74
Discussion
75
DNA REPLICATION
76
DNA REPLICATION
• Maintaining order in a cell also requires the continual surveillance and repair
of its genetic information through a process called proofreading
77
DNA Replication
78
DNA Replication
• Deoxyribonucleic acid (DNA) stores genetic
information
79
DNA Replication
Central Dogma of Molecular Biology
• In all living cells, genetic information flows
from DNA to RNA (transcription) and from
RNA to protein (translation) – an
arrangement known as the central dogma
81
DNA Replication
82
DNA Replication
Structure of the DNA
• The nucleotides are composed of a nitrogen-containing base and a five-carbon
sugar, to which a phosphate group is attached
• For the nucleotides in DNA, the sugar is deoxyribose (hence the name
deoxyribonucleic acid) and the base can be either adenine (A), cytosine (C),
guanine (G), and thymine (T)
83
DNA Replication
• DNA replication occurs in the Synthesis phase (S phase) of the cell cycle. Here, an
exact copy of the DNA helix is produced. This happens with the assistance of
replication enzyme complex called replisomes
84
DNA Replication
• The two strands that make up the parental DNA are bonded to each other by
hydrogen bonds, which can be seen as either a
85
DNA Replication
1. During replication, the old (parental) DNA strands unwind and unzip (i.e., the weak
hydrogen bonds between the two strands break). These two processes are
catalyzed by the enzyme, helicase
86
DNA Replication
2. New complementary nucleotides, which are always present in the nucleus, pair
with the nucleotides in the old strands
- The enzyme DNA polymerase III adds new nucleotides forming new (daughter)
complementary strands. A pairs with T, and C pairs with G
- Also, DNA polymerase proofreads its own work. If an incorrect nucleotide is
accidentally added to a growing strand, the DNA polymerase cleaves it from the strand
and replaces it with the correct nucleotide before continuing
87
DNA Replication
88
DNA Replication
Replication fork
89
DNA REPLICATION ENZYMES/PROTEINS
• Helicase – Helicase binds to the DNA and allows the unwinding/untwisting of
the DNA helix structure. Also, it breaks the hydrogen bonds holding the two
parent DNA strands together to provide two template strands for the synthesis
of new DNA
90
DNA Replication Enzymes/Proteins
• Ligase – This enzyme joins the Okazaki fragments forming the growing lagging
strand
• Gyrase – Gyrase returns the DNA strands into a double helix, and also, zips the
DNA back together
• Telomerase – Each time a cell divides, the telomeres lose a small amount of
DNA and become shorter. Telomerase adds DNA to the telomeres and prevents
the cells from damage and death
91
PROPOSED DNA REPLICATION MODELS
92
Proposed DNA Replication Models
93
Proposed DNA Replication Models
94
Proposed DNA Replication Models
Summary: mosaic
95
Proposed DNA Replication Models
96
DISCUSSION
97
THE CELL CYCLE
• A cell reproduces by carrying out an orderly sequence of events in which it
duplicates its contents and then divides in two
• This sequence of events from the time a cell divides to the time the resulting daughter cells also
divide is called “the cell cycle”
• The cell cycle in higher eukaryotes is carefully regulated by internal and external
signals
- For example, growth factors are external signals received at the plasma membrane
that cause a resting cell to undergo the cell cycle
- When blood platelets release a growth factor, skin fibroblasts in the vicinity finish the
cell cycle, thereby repairing an injury
• Other signals ensure that the stages follow one another in the normal sequence
and that each stage is properly completed before the next stage begins
3
The Cell Cycle
To explain how cells reproduce, it is important that we are able to answer these 3 major
questions
1. How do cells duplicate their contents - including the chromosomes, which carry the
genetic information?
3. How do they coordinate all the steps and machinery required for these two processes?
4
The Cell Cycle
• When appropriate signals are present, a cell doubles its organelles and accumulates
materials needed for DNA synthesis and cell division
• During the cell cycle, there is replication of genetic materials, subsequent mitosis, and
specialization of cells due to existing needs. These processes allow humans to grow
and also repair damaged tissues
• Although, the cell cycle focuses on cell proliferation, many cells in “animals” remain
permanently in a state of quiescence (G0 phase),
- whereas others can resume proliferation if stimulated by appropriate growth factors or
other extracellular signals
5
The Cell Cycle
Proliferative (Labile) cells - these type of cells are constantly going through the cell
cycle. Examples of such cells include:
• Epithelium of skin, Gastrointestinal tract (GIT), Urinary tract, Haematopoietic stem
cells (in the red bone marrow)
Stable cells – cells that do not replicate/through the cell cycle all the time. These type
of cells can initiate the cell cycle when they are stimulated by a strong signal. Examples
of cells include:
• Liver cell (hepatocyte), Epithelium of kidney tubules, Alveolar cells of the lungs
Permanent cells (Amitotic) – once these types of cells have completed the cell cycle,
they do not go through it again. Example of cell include:
• Neurons, Skeletal muscle, Cardiac muscle (myocardium)
6
The Cell Cycle
The cell cycle has 2 major phases
• Interphase
− G1 Phase
− Synthesis Phase (S Phase)
− G2 Phase
• Mitotic phase
− Mitosis
− Cytokinesis
• The passage of animal cells through the cell cycle is regulated primarily by the
extracellular growth factors that signal cell proliferation
• In the presence of the appropriate growth factors, a cell passes the restriction
checkpoint and enters the S phase
7
The Cell Cycle
• Once it has passed through the restriction point, the cell is committed to proceed
through S phase and the rest of the cell cycle, even in the absence of further growth
factor stimulation
• However, if appropriate growth factors are not available in G , progression through the
cell cycle stops at the restriction point
1
• The arrested cell then enters a quiescent phase of the cell cycle called G where they
can remain dormant for long periods of time without proliferating
0
8
INTERPHASE
• Two significant events occur during the interphase: these are replication of DNA and
protein synthesis
1. G1 Phase
• The cell doubles its organelles (mitochondria, ribosomes, etc) and accumulates
materials that will be used in DNA synthesis
• Some of which are proteins, including enzymes (like the replisomes)
• The proliferation of most animal cells is regulated in the G1 phase of the cell cycle
• A decision point in G1, called the restriction checkpoint in animal cells determines the
progression of the cell in the cycle
9
Interphase
10
Interphase
− Cell cycle checkpoints
• Progression through the cell cycle is stimulated by
extracellular signals, such as nutrients and growth
factors
• All events occurring in different stages of the cell
cycle must be coordinated with one another so that
they occur in the appropriate order
Apoptosis
• Any cell that did not successfully complete mitosis and is abnormal undergoes
apoptosis at the restriction checkpoint
• Apoptosis is often defined as programmed cell death because the cell progresses
through a series of events that bring about its destruction
• The cell rounds up and loses contact with its neighbors
• The nucleus fragments and the plasma membrane develops blisters
• Finally, the cell fragments and its bits and pieces are engulfed by white blood cells
and/or neighboring cells
12
Interphase
3. G2 Phase
• This phase is primarily focused on cell growth. For example, the cytoplasm of the
cell increases in size in order to make provision for cell division
• The cell synthesizes proteins that will assist cell division, such as the proteins
found in microtubules
13
MITOTIC PHASE
• After the interphase, the cell enters the M phase where cell division occurs
• There is division of the nucleus (Mitosis) and division of the cytoplasm
(Cytokinesis)
• During mitosis, chromosomes are distributed to two separate nuclei. When
cytokinesis is complete, two daughter cells are present
15
Mitotic Phase
Prophase
• Four major activities occur at this phase that indicate the cell is about to divide
• The two pairs of centrioles outside the nucleus begin moving away from each other
toward opposite ends of the nucleus
• Spindle fibers appear between the separating centriole pairs
• The nuclear envelope begins to fragment, and the nucleolus begins to disappear
• Condensation of the chromatin to sister chromatids
16
Metaphase
• The nuclear envelope is fragmented, and the spindle occupies the region formerly
occupied by the nucleus
• Spindle fibers attach to the centromeres as the chromosomes continue to shorten and
thicken
• The paired chromosomes are now at the equator (center) of the spindle. Metaphase is
characterized by a fully formed spindle, and each chromosome with two sister
chromatids, are aligned at the equator
17
Mitotic Phase
Anaphase
• The sister chromatids separate from each other. Once the chromatids are separated,
they are called chromosomes
• Separation of the sister chromatids ensures that each cell receives a copy of each
type of chromosome and a full complement of genes
• During anaphase, the daughter chromosomes move to the poles of the spindle
• Anaphase is characterized by the movement of chromosomes toward each pole and
thus, to opposite sides of the cell
18
Mitotic Phase
Telophase
• Telophase begins when the chromosomes arrive at the poles. During telophase, the
chromosomes become indistinct chromatin again. The spindle disappears as nucleoli
appear, and nuclear envelope components reassemble in each cell. Telophase is
characterized by the presence of two daughter nuclei
• Cytokinesis is division of the cytoplasm and organelles. In human cells, a slight
indentation called a cleavage furrow passes around the circumference of the cell.
Actin filaments form a contractile ring, and as the ring gets smaller and smaller, the
cleavage furrow pinches the cell in half. As a result each cell becomes enclosed by its
own plasma membrane
19
20
Summary of Mitosis
21
22
BIOLOGICAL RELEVANCE OF THE CELL CYCLE
Tissue repair/ tissue replacement
• Skin fibroblasts are arrested in G0 phase until they are stimulated to divide
- This becomes necessary when repair of damaged tissue resulting from a wound is
required
23
Biological relevance of the cell cycle
Conception and foetal development
• When appropriate signals are present, a cell doubles its organelles and accumulates
materials needed for DNA synthesis and cell division
- During the cell cycle, there is replication of genetic materials, and subsequent
mitosis
• These processes allow humans to grow by ensuring that a cell duplicates to produce
daughter cells of the same kind, and with the same number of diploid chromosomes
- During fertilization, a foetus inherits its genome from both parent gamete cells
(haploid cells) in order to possess a complete human genome, which typically has
46 chromosomes: 23 each from maternal- and paternal sources
• As the foetus develops, mitotic division of the cells occurs in the mother’s uterus to
produce identical cells, and this enable the formation of tissues, organs/organ
systems, and the overall growth and development of the foetus
25
Monosomy 9
Several genes that control cell growth
and division are found on Chromosome 9
26
Trisomy 21
Causes Down Syndrome
Characterised by developmental and intellectual delay
27
DNA REPLICATION
• Deoxyribonucleic acid (DNA) stores genetic
information
30
DNA Replication
31
DNA Replication
Structure of the DNA
32
33
DNA Replication
• Structure of the DNA
• The nucleotides are composed of a nitrogen-containing base and a f ive-carbon
sugar, to which a phosphate group is attached
• Fo r the nuc leo tides in DN A, the sugar is deoxyribo se ( henc e the name
deoxyribonucleic acid) and the base can be either adenine (A), cytosine (C),
guanine (G), or thymine (T)
34
DNA Replication
• DNA replication occurs in the Synthesis phase (S phase) of the cell cycle. Here, an
exact copy of the DNA helix is produced. This happens with the assistance of
replication enzyme complex called replisomes
• The double-stranded structure of the DNA makes replication possible because each
old (parental) DNA strand serves as a template for each new (daughter) strand
• Before replication begins, the two strands that make up the parental DNA are
bonded to each other by hydrogen bonds, which can be seen as either a
- Double bond between A and T, whereas a triple bond between C and G
35
DNA Replication
1. During replication, the old (parental) DNA strands unwind and unzip (i.e., the weak
hydrogen bonds between the two strands break). These two processes are
catalyzed by the enzyme, helicase
36
DNA Replication
2. New complementary nucleotides, which are always present in the nucleus, pair
with the nucleotides in the old strands
• The enzyme DNA polymerase III adds new nucleotides forming new (daughter)
complementary strands. A pairs with T, and C pairs with G
• Also, DNA polymerase proofreads its own work. If an incorrect nucleotide is
accidentally added to a growing strand, the DNA polymerase cleaves it from the strand
and replaces it with the correct nucleotide before continuing
37
DNA Replication
38
DNA Replication
Replication fork
39
DNA REPLICATION ENZYMES/PROTEINS
• Helicase – Helicase binds to the DNA and allows the unwinding/untwisting of
the DNA helix structure. Also, it breaks the hydrogen bonds holding the two
parent DNA strands together to provide two template strands for the
synthesis of new DNA
• Topoisomerase – Prevents tangling and knotting of DNA as the strands are
unzipped
• DNA Polymerase – Is responsible for DNA replication, by adding/pairing
nucleotides to each side of the template strands in the 5′ to 3′ direction to
produce new strands complementary to the parent strand
• Also, DNA Polymerase proofreads its work and corrects nucleotide mismatch
• Is responsible for changing the RNA primers into DNA (changing the base Uracil to into
Thymidine)
40
DNA Replication Enzymes/Proteins
• Telomerase – Each time a cell divides, the telomeres lose a small amount of
DNA and become shorter. Telomerase adds DNA to the telomeres and
prevents the cells from damage and death
41
PROPOSED DNA REPLICATION MODELS
1. Semiconservative replication
42
Proposed DNA Replication Models
43
Proposed DNA Replication Models
44
Proposed DNA Replication Models
Summary: mosaic
45
Proposed DNA Replication Models
46
CELL AND MOLECULAR BIOLOGY
Level 100, Bachelor of Technology
Felix Osei-Boakye
Ph.D Haematology & Transfusion Science (in-view),
MPhil. Haematology, BSc, & Dip. (Med. Lab. Science).
Sunyani Technical University
Department of Medical Laboratory Science
1
THE CELL
2
THE CELL
• Every animal or plant is a vast colony of individual cells, each of which performs a
specialized function that is integrated by intricate systems of cell-to-cell
communication
3
The Cell
• Some require oxygen to live, whereas, for others the gas is deadly
- Some cells consume little/more carbon dioxide (CO2), sunlight, and water as their
raw materials
- Also, others need a complex mixture of molecules produced by other cells
• *
4
The Cell
• Despite the extraordinary diversity of plants and animal species, people have
recognized from time immemorial that these organisms have something in
common that entitles them to be called living organisms
- Sensitive or respond to the environment, capable of reproduction, growth and
development, regulation, homeostasis, and energy processing
• Another property of living cells is the presence of soluble enzymes located in the
cytoplasm
- Cellular enzymes catalyze biosynthesis of the low molecular weight precursors to
protein and nucleic acids
5
The Cell
6
Prokaryotic Cell
• Prokaryotes include cells of two domains, the Archaea and the Bacteria, which
diverged early in evolution
- The Archaea include cells that live in extreme environments that are unusual today
but may have been prevalent in primitive Earth. For example, thermoacidophiles live
in hot sulfur springs with temperatures as high as 80°C and pH values as low as 2
• All prokaryote cell components are located together in the same compartment
- They are made of a single compartment
• Prokaryotic cells are smaller and simpler than most eukaryotic cells, their
genomes are less complex, and they do not contain nuclei
8
Prokaryotic Cell
• The largest and most complex prokaryotes are the Cyanobacteria - bacteria in
which photosynthesis evolved
9
Photograph of a primitive hot spring in East Africa
Hot springs are good sites to find archaea
10
Eukaryotic Cell
11
Eukaryotic Cell
• Like prokaryotic cells, all eukaryotic cells are surrounded by a plasma membrane
and contain ribosomes
• However, eukaryotic cells are much more complex and contain a nucleus and a
variety of cytoplasmic organelles
• The largest and most prominent organelle of eukaryotic cells is the nucleus, with
a diameter of approximately 5μm
• The nucleus contains the genetic information of the cell, which in eukaryotes is
organized as linear rather than circular DNA molecules
• The nucleus is the site of DNA replication and of RNA synthesis; the translation of
RNA into proteins takes place on ribosomes in the cytoplasm
12
Eukaryotic Cell
• Eukaryotic cells are generally much larger than prokaryotic cells, frequently
having a cell volume at least a thousandfold greater
• The larger and more complicated cells of higher eukaryotic organisms (animals,
fungi, plants, and protists) are subdivided into separate compartments and are
called eukaryotic cells.
13
Features that Distinguish Eukaryotic and Prokaryotic Cells
Assignment 1
14
Cellular Organization
- Cells of skeletal muscle, liver, and other tissues may have up to 50 nuclei and are
multinucleate
15
The Plasma Membrane
• Our cells are surrounded by an outer membrane (plasma membrane) that is formed
by phospholipid and protein
• The plasma membrane separates the inside of the cell (cytoplasm) from the
outside
- Therefore, it serves as an interface that allows the internal part of the cell to interact with
the external environment
• The membrane is physically weak and flexible. Most bacterial and plant cells have
hard cell walls, though animal cells usually do not
• The plasma membrane is a phospholipid bilayer with proteins either attached (also
called peripheral proteins) or embedded (also called integral proteins)
16
The Plasma Membrane
17
Cellular Organization
The Plasma Membrane
18
The Plasma Membrane
• Short chains of sugars are attached to the outer surfaces of some protein and
lipid molecules (called glycoproteins and glycolipids, respectively)
- These carbohydrate chains, specific to each cell, mark the cell as belonging to a
particular individual
- Such cell markers account for such characteristics as blood type or why a patient’s
system sometimes rejects an organ transplant
20
Cellular Organization
The Nucleus
• The presence of a nucleus is the principal feature that distinguishes eukaryotic cells
from prokaryotic cells
• DNA replication, transcription, and RNA processing all take place within the
nucleus, whereas, the final stage of gene expression (translation) localized to the
cytoplasm
21
Cellular Organization
The Nucleus
• The unique chemical composition of each person’s DNA forms the basis for DNA
fingerprinting
• The nucleus is separated from the cytoplasm by a double membrane known as the
nuclear envelope, which is continuous with the endoplasmic reticulum
• The nuclear envelope has nuclear pores of sufficient size to permit the passage of
proteins into the nucleus and ribosomal subunits out of the nucleus
• Additionally, the double membrane of the nuclear envelope surrounds and contains
cellular DNA, protecting the vital genetic information contained within its molecules
22
Cellular Organization
Ribosomes
• Ribosomes are composed of two subunits, one large and one small. Each subunit
has its own mix of proteins and rRNA
• Protein synthesis occurs at the ribosomes
• Ribosomes are found free within the cytoplasm either singly or in groups called
polyribosomes (called polysomes for short)
• Ribosomes are often attached to the endoplasmic reticulum, a membranous
system of saccules and channels
• Proteins synthesized by cytoplasmic ribosomes are used inside the cell for various
purposes. Those produced by ribosomes attached to endoplasmic reticulum may
eventually be secreted from the cell
23
Cellular Organization
Endoplasmic Reticulum
• The endoplasmic reticulum (ER), a complicated system of membranous channels
and saccules (flattened vesicles), is physically continuous with the outer
membrane of the nuclear envelope. Rough ER is studded with ribosomes on the
side of the membrane that faces the cytoplasm
• Here proteins are synthesized and enter the ER interior where processing and
modification begin. Some of these proteins are incorporated into membrane, and
some are for export. Smooth ER, which is continuous with rough ER, does not have
attached ribosomes
• Smooth ER synthesizes the phospholipids that occur in membranes and has
various other functions, depending on the particular cell
- In the testes, it produces testosterone, and in the liver it helps detoxify drugs
24
Cellular Organization
Mitochondria
• Are bounded by a double membrane
• The inner membrane is folded to form little shelves called cristae, which project
into the matrix, an inner space filled with a gel-like fluid
• Mitochondria are the site of ATP (adenosine triphosphate) production involving
complex metabolic pathways
- ATP molecules are the common carriers of energy in cells
• *
25
Cellular Organization
Mitochondria
• The mitochondrion is often called the powerhouse of the cell
• Just as a powerhouse burns fuel to produce electricity, the mitochondria convert the
chemical energy of carbohydrate molecules into the chemical energy of ATP
molecules
• In the process, mitochondria use up oxygen and give off carbon dioxide and water
• The oxygen you breathe in enters cells and then mitochondria; the carbon dioxide
you breathe out is released by mitochondria
- Because oxygen is used up and carbon dioxide is released, we say that mitochondria
carry on cellular respiration
26
Cellular Organization
Mitochondria
• Fragments of digested carbohydrate, protein, and lipid enter the mitochondrial
matrix from the cytoplasm
• The matrix contains enzymes for metabolizing these fragments to carbon dioxide
and water
• Energy released from metabolism is used for ATP production, which occurs at the
cristae
- The protein complexes that aid in the conversion of energy are located in an assembly-
line fashion on these membranous shelves
• Many cells use ATP to carry out their specialized functions
- For example, muscle cells use ATP for muscle contraction, which produces movement,
and
- nerve cells use it for the conduction of nerve impulses, which make us aware of our
environment
27
Cellular Organization
The Cytoskeleton
• Several types of filamentous protein structures form a cytoskeleton, and this helps
to maintain the shape of the cell, and either anchors the organelles or assists
their movement as appropriate
• The cytoskeleton includes microtubules, intermediate filaments, and actin filaments
28
Cellular Organization
The Cytoskeleton
b. Intermediate filaments differ in structure and function. Because they are tough
and resist stress, intermediate filaments often form cell-to-cell junctions
• Intermediate filaments join skin cells in the outermost skin layer, the epidermis
c. Actin filaments are long, and extremely thin fibers that usually occur in bundles
or groups
• Actin filaments have been isolated from various types of cells, especially those in
which movement occurs
• Microvilli, which project from certain cells and can shorten and extend, contain actin filaments.
Actin filaments, like microtubules, can assemble and disassemble
29
DISCUSSION
30
TRANSPORT ACROSS THE PLASMA MEMBRANE
31
Transport across the plasma membrane
Simple Diffusion
• Diffusion is the spontaneous movement of simple atoms or molecules from an
area of higher concentration to an area of lower concentration until they are
equally distributed
• Eventually eliminating the concentration difference between the two regions
- To illustrate diffusion, imagine putting a tablet of dye into water
- The water eventually takes on the color of the dye as the dye molecules diffuse
32
Transport across the plasma membrane
Simple Diffusion
• The chemical and physical properties of the plasma membrane allow only a few
types of molecules to enter and exit a cell by simple diffusion
- However, lipid-soluble molecules such as alcohols can diffuse through the membrane
because lipids are the membrane’s main structural components
• Gases can also diffuse through the lipid bilayer; this is the mechanism by which
oxygen enters cells and carbon dioxide exits cells
- For example, consider the movement of oxygen from the lungs to the bloodstream
- When you inhale, oxygen fills the tiny air sacs (alveoli) within your lungs. Neighboring
lung capillaries contain red blood cells with a very low oxygen concentration
- Oxygen diffuses from the area of higher (oxygen) concentration to the area of lower
(oxygen) concentration: first through alveolar cells, then lung capillary cells, and
finally into the red blood cells
33
Transport across the plasma membrane
Simple Diffusion
• When atoms or molecules diffuse from areas of higher to lower concentration
across plasma membranes, no cellular energy is involved
• Instead, kinetic or thermal energy of matter is the energy source for diffusion
34
Transport across the plasma membrane
Osmosis
• In osmosis, there is the movement of solvent molecules across a
semipermeable membrane, from a region of higher water concentration to a
region of lower water concentration
• Water molecules move more rapidly through the membrane of a cell than
dissolved ions or small polar organic solutes, which are considered
nonpenetrating
- Because of this difference in the penetrability of water versus solutes through the
plasma membrane, the membrane is said to be semipermeable
35
Transport across the plasma membrane
Osmosis
• Osmosis occurs whenever an unequal concentration of water exists on either
side of a selectively permeable membrane
- In a solution, water is more concentrated when it contains fewer dissolved
substances, or solutes, (and thus is closest to pure water)
- Water is less concentrated as solute concentration increases
• (Recall that a selectively permeable membrane allows water to pass freely, but
not most dissolved substances)
36
Transport across the plasma membrane
Osmosis
37
Transport across the plasma membrane
Osmosis
38
Transport across the plasma membrane
Osmosis
(a) A cell placed in a
hypotonic solution (one
having a lower solute
concentration than the cell)
swells because of a net gain
of water by osmosis
Facilitated Transport
• Substances always diffuse across the plasma membrane, when the concentrations
of substances on either sides/regions of the membrane are different
• However, most solutes do not simply diffuse across a plasma membrane
- Also, they do not always diffuse through the lipid bilayer or through a channel
- Instead, they are transported by means of protein carriers within the membrane
• The cell does not require energy for this type of transport because the molecules
are moving down their concentration gradient
40
Transport by Carriers
Facilitated Transport
• Facilitated diffusion mediates the entry and exit of polar solutes, such as sugars
and amino acids, that do not penetrate the lipid bilayer
• Unlike ion channels, which can conduct millions of ions per second, most
facilitative transporters can move only hundreds to thousands of solute molecules
per second across the membrane
• The activity of facilitative transporters can be regulated, like enzymes and ion
channels
41
Transport by Carriers
Facilitated Transport
• In many cases, the diffusing
substance first binds selectively to a
membrane-spanning protein, called
a facilitative transporter, that
facilitates the transport/diffusion
process
Active Transport
• This is an energy-driven process where membrane proteins transport molecules
or ions across a cell membrane from a region of lower concentration to a region of
higher concentration, against the concentration gradient
• Active transport requires a protein carrier and the use of cellular energy obtained
from the breakdown of ATP
- There is one type of pump that is active in all cells but is especially associated with
nerve and muscle cells
- This pump moves sodium ions (Na+) to the outside of the cell and potassium ions (K+) to
the inside of the cell
*
43
Transport by Carriers
Active Transport
• When ATP is broken down, energy is released, and in this case the energy is
used by a carrier to carry out active transport
• Therefore, cells involved in active transport have a large number of mitochondria
near the plasma membrane at which active transport is occurring
44
DISCUSSION
45
Transport across the plasma membrane
• Eukaryotic cells are also able to ingest large particles (such as bacteria) and
the uptake of fluids or macromolecules in small vesicles from the surrounding
medium by a distinct process called endocytosis
46
Transport across the plasma membrane
• During exocytosis, a vesicle fuses with the plasma membrane as secretion occurs
47
Transport across the plasma membrane
48