Topic 1.

1: Cell Theory
Cell Theory Functions of Life

According to the cell theory: Organisms consisting of only one cell carry
out all the life functions in that single cell
1.  Living organisms are composed of cells (or cell products)
2.  The cell is the smallest unit of independent life
•  Metabolism
3.  Cells can only arise from pre-existing cells
•  Reproduction
•  Sensitivity
Caveats to the cell theory include:
•  Homeostasis
•  Striated muscle – composed of fused cells that are multinucleated •  Excretion
•  Giant algae – unicellular organisms that are very large in size (~7 cm) •  Nutrition
•  Aseptate hyphae – lack partitioning and have a continuous cytoplasm •  Growth

Cell Size

Surface area to volume ratio is important in the limitation of cell size Small SA:Vol Ratio
Cells need to exchange materials with the environment in order to produce ︎ metabolic rate
the chemical energy required for survival (via metabolism) ➡︎ material exchange
•  The rate of metabolism is a function of a cell’s mass / volume Low survival chances
•  The rate of material exchange is a function of a cell’s surface area
Large SA:Vol Ratio

As a cell grows, volume (units3) increases faster than surface area (units2) ➡︎ metabolic rate
•  If metabolic requirements exceed material exchange, a cell will die ︎ material exchange
•  Hence, cells must stay small or increase their SA:Vol ratio to survive High survival chances

Magnification Microscopes

Calculating Magnification (MIA): Light microscopes use lenses to bend light

Magnification = Image Size ÷ Actual Size •  Can view living specimens in natural colour
•  Have lower magnification and resolution
Calculating Actual Size (AIM):
Electron microscopes use electromagnets to focus electrons
Actual Size = Image Size ÷ Magnification
•  Can only view dead specimens in monochrome
•  Have higher magnification and resolution
Cellular Organization
•  Can show cross-sections (TEM) or surface renderings (SEM)
In multicellular organisms:
•  Cells may be grouped together to form tissues Emergent Properties
•  Tissues may interact to form functional organs
An emergent property is a function that is present in multicellular
•  Organs may combine to form body systems
organisms, but is not present in its individual component cells

Emergent properties arise from synergistic interactions between

the individual cells to produce entirely new aggregate functions
An example of an emergent property is the increased levels of
antibiotic resistance that can be seen in bacterial biofilms
Muscle Cardiac Heart Vascular
(Cell) (Tissue) (Organ) (System) ‘The whole is greater than the sum of its parts’ – Aristotle
 Topic 1.1: Cell SPECIALIZATION
Stem Cells

Stem cells are unspecialised cells that have two key qualities:
Embryonic Totipotent
1.  Self-Renewal – They can continuously divide and replicate Stem Cells
2.  Potency – They have the capacity to differentiate
Pluripotent
Fetal
There are four main types of stem cells during human development: Stem Cells Multipotent
•  Totipotent – Can form any cell type, as well as extra-embryonic tissue
Adult Unipotent
•  Pluripotent – Can form any cell type (e.g. embryonic stem cells)
Stem Cells
•  Multipotent – Can differentiate into closely related cell types
•  Unipotent – Cannot differentiate, but are capable of self-renewal Types of Stem Cells

Stem Cell Therapy Therapeutic Examples

Stem cells can replace damaged or diseased cells with healthy ones Example Condition Treatment

The therapeutic use of stem cells involves: Stargardt’s Macular Replace defective
disease degeneration retinal cells
•  Harvesting stem cells from appropriate sources
•  Using biochemical solutions to trigger cell differentiation Parkinson’s Death of Replace damaged
•  Surgically implanting new cells into patient's own tissue disease nerve tissue nerve cells
•  Suppressing the host immune system to prevent rejection
Cancer of Replacement of
•  Monitoring new cells to ensure they do not become cancerous Leukemia
the blood bone marrow

Ethics of Stem Cell Use

Source Growth Potential Tumour Risk Harvesting Disadvantages

Can be generated Requires destruction of the embryo

Embryo High (pluripotent) Higher risk
artificially by SCNT (results in the loss of a potential life)

Umbilical Easily obtained and Cells must be stored from birth at cost
Low (multipotent) Lower risk
Cord Blood stored / preserved (raises issues of financial accessibility)

Adult Tissue Low (multipotent) Lower risk Invasive to extract May be restrictions in scope / availability

Differentiation Gene Packaging

All cells of an organism contain an identical genome – each cell Within the nuclei of eukaryotic cells, gene instructions
contains the entire set of genetic instructions for that organism (DNA) are packaged with proteins as chromatin

Differentiation involves the expression of some genes and not •  Active genes are loosely packed as euchromatin
others in the cell’s genome (i.e. selective gene expression) •  Inactive genes are packed tight as heterochromatin
The activation of different genes within a given cell will cause it Nucleus Micrograph:
to develop differently from other cells (i.e. cell specialisation)
Heterochromatin (inactive)
Red cell (gene A)

Green cell (gene B) Euchromatin (active)

Single cell
 Topic 1.2: PRokAryotic Cells
Prokaryotic Cell Structure

Prokaryotes are organisms whose cells lack a nucleus

•  They belong to the kingdom Monera (i.e. bacteria) Pilus
Cytoplasm
Prokaryotic cells share the following structures: Genophore Cell wall
•  A single, circular DNA molecule (genophore)
•  A peptidoglycan cell wall and 70S ribosomes Cell membrane
70S Ribosome
Prokaryotic cells may also contain the following:
•  Pili (for attachment or bacterial conjugation) Plasmid
Flagellum
•  Flagella (a long whip-like tail for movement)
•  Plasmids (autonomous DNA molecules) Glycocalyx

Prokaryote Micrographs

Nucleoid (yellow) Bacterial Conjugation (pili = red) Cell Wall (purple) Flagella (white)

Prokaryotic versus Eukaryotic Cells Bacterial Cell Division

Prokaryotic and eukaryotic cells differ Prokaryotes divide via a process of asexual
according to a number of key features: reproduction known as binary fission
•  DNA (composition and structure)
•  Organelles (types present and sizes) In this process
•  Reproduction (mode of cell division) •  The circular DNA is copied
•  Average Size (exceptions may exist) •  The DNA loops attach to the membrane
•  The cell elongates, separating the loops
Prokaryote Eukaryote •  Cytokinesis occurs to form two cells

DNA is naked DNA bound to protein

DNA DNA is circular DNA is linear
Usually no introns Usually contains introns DNA replication

No nucleus Has a nucleus

Organelles Cell growth
70S ribosomes 80S ribosomes

Via binary fission Via mitosis and meiosis

Reproduction Cytokinesis
Single chromosome Paired chromosomes

Average Size Smaller (~1 – 5 µM) Larger (~10 – 100 µM)

 Topic 1.2: EuKAryotic Cells
Eukaryotic Cell Structure

Golgi body Smooth ER Nucleus Rough ER

Lysosome
Mitochondrion

Rough ER Cytosol
Smooth ER
Nucleolus Ribosome
Cytosol
(80S)
Nucleus
Membrane
Golgi body Membrane
80S Ribosome
Mitochondrion Vacuole Chloroplast Cell wall

Animal Cell Plant Cell

Eukaryote Micrographs

Golgi complex Chloroplast

Animal Cell (exocrine gland cell) ER (rough) Mitochondrion Plant Cell (palisade mesophyll)

Organelles Animal versus Plant Cells

Organelles are compartmentalised structures that serve specific purposes Animal Cells Plant Cells

Examples of eukaryotic organelles include: ︎No chloroplast Have chloroplast

•  80S ribosomes – Responsible for protein synthesis (translation)
•  Nucleus – Stores genetic information (site of transcription) No cell wall Cell wall (cellulose)
•  Mitochondria – Site of aerobic respiration (ATP production)
•  Endoplasmic reticulum – Transports materials between organelles No plasmodesmata Plasmodesmata
•  Golgi complex – Sorts, stores, modifies & exports secretory products
•  Centrosomes – Involved in cell division (mitosis and meiosis) Temporary vacuoles Large central vacuole

Organelles found only in specific cell types include: Cholesterol present No cholesterol in
•  Chloroplasts – Site of photosynthesis (plant cells only) in the cell membrane the cell membrane
•  Lysosomes – Breakdown of macromolecules (animal cells)
Glucose → glycogen Glucose → starch
 Topic 1.3: membrAne Structure
Phospholipid Bilayer

Structure of Phospholipids:
•  Contain a polar (hydrophilic) head composed of phosphate (+ glycerol) Polar head
Hydrophilic
•  Contain two non-polar (hydrophobic) tails, each composed of a fatty acid chain
•  Hence, phospholipids are amphipathic (have hydrophilic and hydrophobic parts) Non-polar tail
Hydrophobic
Arrangement in Membranes:
•  Phospholipids spontaneously arrange into a bilayer Phospholipid
•  The hydrophilic phosphate heads face out into the surrounding solution, while
the hydrophobic fatty acid tails face inwards and are shielded from the polar fluids

Properties of the Phospholipid Bilayer:

•  The bilayer is held together by weak hydrophobic interactions between the tails
•  Individual phospholipids can move within the bilayer (fluidity and flexibility)
•  Amphipathic properties restrict passage of certain substances (semi-permeable) Bilayer

Cholesterol Membrane Proteins

Cholesterol is a fundamental component of animal cell membranes Membrane proteins are diverse in terms of
•  It is not present in plant cell membranes (as they have a rigid cell wall) their structure and position in a membrane
Cholesterol reduces membrane fluidity and permeability to some solutes Membrane proteins serve many functions:
•  It also anchors certain peripheral proteins and prevents crystallization
•  Junctions
•  Enzymes
•  Transport
•  Recognition
Cholesterol •  Anchorage
(amphipathic) •  Transduction

Fluid Mosaic Model Membrane Models

Cell membranes are represented as a fluid-mosaic model Membranes appear trilaminar when viewed with an electron
•  Fluid – membrane components can move position microscope (trilaminar = three distinct layers)
•  Mosaic – phospholipid bilayer is embedded with protein
Davson-Danielli proposed a model whereby a phospholipid
This model was proposed by Singer-Nicolson in 1972, bilayer was flanked by two protein layers (sandwich model)
following the falsification of the Davson-Danielli model
This model was falsified based on the following findings:
integral protein •  Fluorescent tagging showed the proteins are mobile
cholesterol
•  Not all membranes have a constant lipid : protein ratio
•  Freeze fracturing identified transmembrane proteins

phospholipid
peripheral protein Trilaminar appearance Sandwich Model
 Topic 1.4: membrAne TrAnsport
Properties of Membranes Types of Membrane Transport

Cell membranes have two key properties Membrane transport can either be:
•  Semi-permeable (only certain things can cross) •  Passive (along concentration gradient, no ATP expenditure)
•  Selective (membranes can regulate material passage) •  Active (against concentration gradient, ATP is required)

Passive Transport

Simple Diffusion Facilitated Diffusion

The net movement of particles from a region of higher The passive movement of molecules across a cell membrane
concentration to a region of lower concentration (i.e. along via the aid of a membrane protein (carrier / channel protein)
the gradient) until equilibrium is reached •  Involves large / charged molecules (e.g. ions, glucose, etc.)
•  Involves small / lipophilic molecules (e.g. O2, CO2, steroids) •  E.g. Voltage-gated channels control the flow of ions in neurons

High [ ] Low [ ] Protein Channel Carrier Protein

Osmosis Osmolarity

The net movement of water molecules across a semi-permeable Osmolarity is a measure of solute concentration
membrane from a region of low solute concentration to a region
Solutions can be measured as:
of higher solute concentration (diffusion of free water molecules)
•  Hypertonic: High solute concentration (gains water)
Low solute concentration High solute concentration •  Hypotonic: Low solute concentration (loses water)
12 H2O total ; 12 H20 free 12 H2O total ; 0 H2O free •  Isotonic: Same solute concentration (no net flow)

net

Hypertonic Isotonic Hypotonic

Active Transport Vesicular Transport

Active transport uses energy (ATP) to move molecules The fluidity of the plasma membrane allows it to break and
against a concentration gradient (i.e. from low to high) reform around certain materials (this process requires ATP)
•  Molecule binds to a transmembrane protein pump •  Exocytosis: Materials released from a cell via vesicles
•  Hydrolysis of ATP causes a conformational change, •  Endocytosis: Materials internalised within a vesicle
translocating the molecule across the membrane
•  E.g. Sodium-potassium pumps move ions in neuron Intracellular vesicles can move materials between cell organelles
•  E.g. rough ER → Golgi complex → plasma membrane
Sometimes molecules are passively coupled to an
actively transported molecule (co-transport)
•  Symport: Both molecules move the same direction
•  Antiport: Molecules move in opposite directions
 Topic 1.5: Origin of Cells
Abiogenesis

The formation of living cells from non-living materials

(abiogenesis) is theorised to involve 4 four key processes:
Inorganic Organic Polymer
•  Non-living synthesis of simple organic molecules compounds monomers
•  Assembly of organic molecules into complex polymers
•  Formation of polymers that can self-replicate
•  Packaging of molecules into membranes to create an
internal chemistry different from the surroundings
Self-replication
The Miller-Urey experiment replicated the conditions of a
pre-biotic Earth in order to synthesize organic molecules Formation of cell

Biogenesis

Abiogenesis requires specific conditions in order to proceed Methodology Control Results Experimental
•  Including a reducing atmosphere (no oxygen) and either
high temperatures (>100ºC) or electrical discharges

As these conditions no longer commonly exist on Earth,

cells can only be formed from division of pre-existing cells
heat no growth growth
This law of biogenesis was demonstrated by Louis Pasteur
Broth boiled to Condensation Break to expose
•  Broths were stored in sealed vessels that were sterilised
kill organisms seals the flask contaminants
•  Bacterial growth occurred if vessel was unsealed, but
did not occur if vessel stayed sealed (no contamination) Conclusion: Cells only arise from pre-existing cells

Endosymbiosis Oxygenation of Earth

Eukaryotic cells are believed to have evolved from aerobic The appearance of photosynthetic organisms lead to the
prokaryotes that were engulfed by endocytosis rapidly increasing oxygenation of the Earth’s environment

The engulfed cell remained undigested and contributed new Oceans

functionality to the engulfing cell (i.e. it became an organelle) •  Originally, Earth’s oceans had high levels of dissolved
iron (released from crust by underwater volcanic vents)
•  Oxygen chemically reacted with the iron to form an
insoluble precipitate (iron oxide)

Ancestral Endosymbiosis Ancestral Rock Deposition

Prokaryote Eukaryote •  Insoluble iron formed banded iron formations (BIFs)
•  These deposits are not commonly found in rock that is
Chloroplasts and mitochondria arose via endosymbiosis: younger than 1.8 billion years (hence, identifies when
•  Membranes (have a double membrane) photosynthetic organisms first evolved)
•  Antibiotics (show susceptibility)
•  DNA (have naked and circular DNA) Atmosphere
•  Division (occurs via a fission-like process) •  When dissolved iron was completely consumed, oxygen
•  Ribosomes (have 70S ribosomes) started accumulating in the anoxic atmosphere
 Topic 1.6: Cell Division
Cell Cycle

The cell cycle is an ordered set of events that culminates in cell division
M phase
C Interphase
T
A G1
An active phase of the cell cycle where many metabolic reactions occur
M Growth and
•  Consists of G1, S and G2 stages
metabolism
P
G2 S M phase
and
Growth Replication The period of a cell cycle in which the cell and contents divide
preparation of DNA
•  Consists of mitosis (P, M, A, T) and cytokinesis
Interphase
Some cells may also enter a non-proliferative quiescent phase (G0)

Interphase Supercoiling

Normal metabolism cannot occur during M phase, so key During mitosis, chromatin condenses via supercoiling to
events must occur during interphase to prepare for division: become tightly packed chromosomes
•  Due to replication (S phase), chromosomes consist of
•  DNA replication (during S phase)
identical sister chromatids (joined at a centromere)
•  Organelle duplication
•  Cell growth
•  Transcription / translation S phase Mitosis
•  Obtaining nutrients
•  Respiration (cellular)

Mitosis Cytokinesis

Mitosis is the division of a diploid nucleus Cytokinesis is the process of cytoplasm division, whereby a cell splits in two
into two genetically identical diploid nuclei •  It occurs concurrently with telophase and differs in plants and animals

This process of cell cloning is needed for Animals:

many important processes: •  Microtubules form a concentric ring and
contract towards the centre (centripetal)
•  Tissue repair
•  Organism growth Plants:
•  Asexual reproduction •  Vesicles form at the cell centre and fuse
•  Development of embryos outwards to form a cell plate (centrifugal)

Mitotic Index Mitosis Micrographs

The mitotic index is a measure of the proliferative

Prophase Metaphase Anaphase Telophase
status of a cell population (i.e. number of dividing cells)

The mitotic index will be elevated during growth and

repair processes and acts as a prognostic tool for cancer

Cells in mitosis*
Mitotic Index =
Total number of cells
*Mitotic cells have no nucleus and have visible chromosomes
 Topic 1.6: Cell cycle RegulAtion
Cell Cycle Checkpoints Cyclins

A cell cycle contains numerous checkpoints that ensure Cyclins are proteins that control progression of the cell cycle
the fidelity and viability of continued cell divisions
•  Cyclins bind to cyclin dependent kinases (CDKs)

G1 checkpoint •  The activated complex phosphorylates proteins involved

•  Monitors potential growth conditions (nutrients, etc.) in specific cell cycle events (e.g. centrosome duplication)
•  Assesses level of DNA damage (from UV, etc.) •  After the event has occurred, the cyclin is degraded and
the cyclin dependent kinase is rendered inactive
G2 checkpoint
•  Monitors state of pre-mitotic cell (suitable size, etc.) Cyclin Cyclin active
Cyclin
•  Identifies and repairs any DNA replication errors P P
CDK CDK
Metaphase checkpoint CDK
•  Ensures proper alignment (prevents aneuploidy) Target protein

Cancer Cancer Development

Cancers are diseases caused by uncontrolled cell division Cancers can be caused by many different factors:
•  The resulting abnormal cell growths are called tumors
Mutagens
Tumor cells may remain in their original location (benign) Mutagens are agents that change the genetic material of cells
or spread and invade neighboring tissues (malignant) •  These agents may be either physical (e.g. UV), chemical
(e.g. arsenic) or biological in origin (e.g. certain viruses)
Metastasis is the spread of cancer from an original site to •  Mutagens that cause cancer are classified as carcinogens
a new body location (forming a secondary tumor)
Genetics
Most cancers are caused by mutations to two classes of genes:
•  Proto-oncogenes stimulate cell growth and proliferation
•  Tumor suppressor genes repress cell cycle progression
normal cancer
uncontrolled
cell cell tumor Proto-oncogene mutations create cancer-causing oncogenes
divisions

Cell Death Smoking

The death of a cell may occur by one of two mechanisms: There is a strong positive correlation between the
frequency of smoking and the incidence of cancer
Necrosis (uncontrolled ‘cell homicide’)
•  Cigarette smoke contains >60 known carcinogens
•  The cell loses functional control due to injury, toxins, etc.
•  There is a destabilization of the membranes, leading to swelling
500
•  The cell bursts and releases its contents (causing inflammation)
400
Incidence of cancer

Apoptosis (programmed ‘cell suicide’)

(per 100,000 men)

•  It is a controlled event triggered by mitochondrial proteins 300

•  Cell contents are packaged in membranous protrusions (blebs) 200

•  The cell fragments into apoptotic bodies which are recycled
100

Disintegration Fragmentation
0
10 20 30 40

NECROSIS APOPTOSIS Cigarettes per day

 Topic 1.6: STAGES of miTosis
Stage Diagram Key Events

•  DNA is uncondensed (chromatin)

Before: After:
Interphase
•  DNA is replicated (S phase) to form
(2n) S phase
genetically identical sister chromatids

•  Cell grows in size and organelles are

duplicated (G1 and G2)

Nuclear •  DNA supercoils and condenses

membrane (forms visible chromosomes)
Prophase dissolves
•  Nuclear membrane dissolves
(2n)
Centrosomes
move to poles •  Centrosomes move to poles and
begin to produce spindle fibres

•  Centrosome spindle fibres attach to

Spindle fibres
the centromere of each chromosome

Metaphase •  Spindle fibres contract and move the

(2n) chromosomes towards the cell centre
•  Chromosomes form a line along the
M = Middle
equator (middle) of the cell

Chromatids
•  Spindle fibres continue to contract
•  Sister chromatids separate and move
Anaphase
to opposite sides of the cell
(2n → 4n)
•  Sister chromatids are now regarded as
A = Apart two separate chromosomes

Nuclear
membranes •  Chromosomes decondense
reform (DNA forms chromatin)
Telophase
•  Nuclear membranes form around the
(4n)
two identical chromosome sets
•  Cytokinesis occurs concurrently

•  Cytoplasmic division occurs to divide

the cell into two daughter cells
Cytokinesis
•  Each daughter cell contains one copy
(2n × 2)
of each identical sister chromatid
•  Daughter cells are genetically identical