Ultrastructure of cells
Prokaryotes
Prokaryotes are organisms whose cells lack a nucleus ('pro' = before ; 'karyon' =
nucleus)
They belong to the kingdom Monera and have been further classified into two distinct
domains:
Archaebacteria – found in extreme environments like high temperatures, salt
concentrations or pH (i.e. extremophiles)
■ Eubacteria – traditional bacteria including most known pathogenic forms (e.g. E.
coli, S. aureus, etc.)
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Prokaryotic Features
Prokaryotic cells will typically contain the following cellular components:
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Cytoplasm – internal fluid component of the cell
Nucleoid – region of the cytoplasm where the DNA is located (DNA strand is
circular and called a genophore)
Plasmids – autonomous circular DNA molecules that may be transferred
between bacteria (horizontal gene transfer)
Ribosomes – complexes of RNA and protein that are responsible for polypeptide
synthesis (prokaryote ribosome = 70S)
Cell membrane – Semi-permeable and selective barrier surrounding the cell
Cell wall – rigid outer covering made of peptidoglycan; maintains shape and
prevents bursting (lysis)
Slime capsule – a thick polysaccharide layer used for protection against
dessication (drying out) and phagocytosis
Flagella – Long, slender projections containing a motor protein that enables
movement (singular: flagellum)
Pili – Hair-like extensions that enable adherence to surfaces (attachment pili) or
mediate bacterial conjugation (sex pili)
They are simple unicellular organisms, with no internal compartmentalisation, no nucleus and
no membrane-bound organelles. All metabolic processes thus occur within the cytoplasm. They
have 70S Ribosomes.
Cell division in Prokaryotes
Prokaryotes reproduce by binary fission (a type of cell division) to produce two genetically
identical cells.
Binary fission is a form of asexual reproduction used by prokaryotic cells
In the process of binary fission:
The circular DNA is copied in response to a replication signal
■ The two DNA loops attach to the membrane
■ The membrane elongates and pinches off (cytokinesis), forming two cells
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Overview of Binary Fission and Rate of Bacterial Growth
Prokaryotic Cell
Key Features:
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Pili – shown as single lines
Flagella – shown as thicker and significantly longer lines than the pili
Ribosomes – labelled as 70S
Cell wall – labelled as being composed of peptidoglycan; thicker than cell
membrane
Shape – appropriate for bacteria chosen (e.g. E. coli is a rod-shaped bacillus)
Size – appropriate dimensions (e.g. length of cell twice the width)
Eukaryotes
Eukaryotes are organisms whose cells contain a nucleus (‘eu’ = good / true ; ‘karyon’ =
nucleus)
They have a more complex structure and are believed to have evolved from prokaryotic
cells (via endosymbiosis)
Eukaryotic cells are compartmentalised by membrane-bound structures (organelles)
that perform specific roles
Eukaryotes can be divided into four distinct kingdoms:
Protista – unicellular organisms; or multicellular organisms without specialised
tissue
■ Fungi – have a cell wall made of chitin and obtain nutrition via heterotrophic
absorption
■ Plantae – have a cell wall made of cellulose and obtain nutrition autotrophically
(via photosynthesis)
■ Animalia – no cell wall and obtain nutrition via heterotrophic ingestion
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Typical Structure of an Animal Cell
Typical Structure of a Plant Cell
Prokaryotic Cell
Animal Cell
Key Features:
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Nucleus – shown as double membrane structure with pores
Mitochondria – double membrane with inner one folded into cristae ; no larger
than half the nucleus in size
Golgi apparatus – shown as a series of enclosed sacs (cisternae) with vesicles
leading to and from
Endoplasmic reticulum – interconnected membranes shown as bare (smooth
ER) and studded (rough ER)
Ribosomes – labelled as 80S
Cytosol – internal fluid labelled as cytosol (‘cytoplasm' is all internal contents
minus the nucleus)
Plant Cell
Key Features:
Vacuole – large and occupying majority of central space (surrounded by
tonoplast)
■ Chloroplasts – double membrane with internal stacks of membrane discs (only
present in photosynthetic tissue)
■ Cell wall – labelled as being composed of cellulose ; thicker than cell membrane
■ Shape – brick-like shape with rounded corners
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Organelles are specialised sub-structures within a cell that serve a specific function
Prokaryotic cells do not typically possess any membrane-bound organelles, whereas
eukaryotic cells possess several
Universal Organelles (prokaryote and eukaryote):
Ribosomes
Structure: Two subunits made of RNA and protein; larger in eukaryotes (80S) than
prokaryotes (70S)
Function: Site of polypeptide synthesis (this process is called translation)
Cytoskeleton
Structure: A filamentous scaffolding within the cytoplasm (fluid portion of the cytoplasm
is the cytosol)
Function: Provides internal structure and mediates intracellular transport (less
developed in prokaryotes)
Plasma membrane
Structure: Phospholipid bilayer embedded with proteins (not an organelle per se, but a
vital structure)
Function: Semi-permeable and selective barrier surrounding the cell
Eukaryotic Organelles (animal cell and plant cell):
Nucleus
Structure: Double membrane structure with pores; contains an inner region called a
nucleolus
Function: Stores genetic material (DNA) as chromatin; nucleolus is site of ribosome
assembly
Endoplasmic Reticulum
Structure: A membrane network that may be bare (smooth ER) or studded with
ribosomes (rough ER)
Function: Transports materials between organelles (smooth ER = lipids ; rough ER =
proteins)
Golgi Apparatus
Structure: An assembly of vesicles and folded membranes located near the cell
membrane
Function: Involved in the sorting, storing, modification and export of secretory products
Mitochondrion
Structure: Double membrane structure, inner membrane highly folded into internal
cristae
Function: Site of aerobic respiration (ATP production)
Peroxisome
Structure: Membranous sac containing a variety of catabolic enzymes
Function: Catalyses breakdown of toxic substances (e.g. H2O2) and other metabolites
Centrosome
Structure: Microtubule organising centre (contains paired centrioles in animal cells but
not plant cells)
Function: Radiating microtubules form spindle fibres and contribute to cell division
(mitosis / meiosis)
Plant Cells Only
Chloroplast
Structure: Double membrane structure with internal stacks of membranous discs
(thylakoids)
Function: Site of photosynthesis – manufactured organic molecules are stored in
various plastids
Vacuole (large and central)
Structure: Fluid-filled internal cavity surrounded by a membrane (tonoplast)
Function: Maintains hydrostatic pressure (animal cells may have small, temporary
vacuoles)
Cell Wall
Structure: External outer covering made of cellulose (not an organelle per se, but a vital
structure)
Function: Provides support and mechanical strength; prevents excess water uptake
Animal Cells Only
Lysosome
Structure: Membranous sacs filled with hydrolytic enzymes
Function: Breakdown / hydrolysis of macromolecules (presence in plant cells is subject
to debate)
Membrane Structure
Structure of Phospholipids:
Consist of a polar head (hydrophilic) composed of a glycerol and a phosphate
molecule
■ Consist of two non-polar tails (hydrophobic) composed of fatty acid
(hydrocarbon) chains
■ Because phospholipids contain both hydrophilic (water-loving) and lipophilic
(fat-loving) regions, they are classed as amphipathic
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Arrangement in Membranes:
Phospholipids spontaneously arrange into a bilayer
■ The hydrophobic tail regions face inwards and are shielded from the surrounding
polar fluids, while the two hydrophilic head regions associate with the cytosolic
and extracellular fluids respectively
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Properties of the Phospholipid Bilayer:
The bilayer is held together by weak hydrophobic interactions between the tails
■ Hydrophilic / hydrophobic layers restrict the passage of many substances
■ Individual phospholipids can move within the bilayer, allowing for membrane
fluidity and flexibility
■ This fluidity allows for the spontaneous breaking and reforming of membranes
(endocytosis / exocytosis)
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The Fluid Mosaic Model
Typical exam drawing question:
Cholesterol in membranes
Cholesterol is a type of liquid, but is not a fat or oil. It belongs to the group called steroids.
Its role in the phospholipid bilayer:
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Cholesterol forms an integral part of an animal membrane and plays an important role in
controlling membrane fluidity and permeability to some solutes.
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The cholesterol in the membrane restricts the movement of phospholipids and other
molecules, thus reducing membrane fluidity.
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At low temperatures, it disrupts the regular packing of the hydrocarbon tails of
phospholipid molecules, which prevents the solidification of the membrane. This enables
the membrane to stay more fluid at lower temperatures, allowing the membrane to
function properly.
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It reduces membrane permeability to hydrophilic molecules and ions such as sodium
and hydrogen.
Membrane Proteins
Phospholipid bilayers are embedded with proteins, which may be either permanently or
temporarily attached to the membrane
Integral proteins are permanently attached to the membrane and are typically
transmembrane (they span across the bilayer)
■ Peripheral proteins are temporarily attached by non-covalent interactions and
associate with one surface of the membrane
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Structure of Membrane Proteins
The amino acids of a membrane protein are localised according to polarity:
Non-polar (hydrophobic) amino acids associate directly with the lipid bilayer
■ Polar (hydrophilic) amino acids are located internally and face aqueous solutions
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Transmembrane proteins typically adopt one of two tertiary structures:
Single helices / helical bundles
■ Beta barrels (common in channel proteins)
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Functions of Membrane Proteins
Membrane proteins can serve a variety of key functions:
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Junctions – Serve to connect and join two cells together
Enzymes – Fixing to membranes localises metabolic pathways
Transport – Responsible for facilitated diffusion and active transport
Recognition – May function as markers for cellular identification
Anchorage – Attachment points for cytoskeleton and extracellular matrix
Transduction – Function as receptors for peptide hormones
Mnemonic: Jet Rat
Membrane Protein Functions
Membrane Transport
Cellular membranes possess two key qualities:
They are semi-permeable (only certain materials may freely cross – large and
charged substances are typically blocked)
■ They are selective (membrane proteins may regulate the passage of material
that cannot freely cross)
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Movement of materials across a biological membrane may occur either actively or
passively
Passive Transport
Passive transport involves the movement of material along a concentration gradient
(high concentration ⇒ low concentration)
Because materials are moving down a concentration gradient, it does not require the
expenditure of energy (ATP hydrolysis)
There are three main types of passive transport:
Simple diffusion – movement of small or lipophilic molecules (e.g. O2, CO2, etc.)
■ Osmosis – movement of water molecules (dependent on solute concentrations)
■ Facilitated diffusion – movement of large or charged molecules via membrane
proteins (e.g. ions, sucrose, etc.)
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Active Transport
Active transport involves the movement of materials against a concentration gradient
(low concentration ⇒ high concentration)
Because materials are moving against the gradient, it requires the expenditure of
energy (e.g. ATP hydrolysis)
There are two main types of active transport:
Primary (direct) active transport – Involves the direct use of metabolic energy
(e.g. ATP hydrolysis) to mediate transport
■ Secondary (indirect) active transport – Involves coupling the molecule with
another moving along an electrochemical gradient
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Active transport uses energy to move molecules against a concentration gradient
This energy may either be generated by:
The direct hydrolysis of ATP (primary active transport)
■ Indirectly coupling transport with another molecule that is moving along its
gradient (secondary active transport)
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Active transport involves the use of carrier proteins (called protein pumps due to their
use of energy)
A specific solute will bind to the protein pump on one side of the membrane
■ The hydrolysis of ATP (to ADP + Pi) causes a conformational change in the
protein pump
■ The solute molecule is consequently translocated across the membrane (against
the gradient) and
The axons of nerve cells transmit electrical impulses by translocating ions to create a
voltage difference across the membrane
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■ At rest, the sodium-potassium pump expels sodium ions from the nerve cell,
while potassium ions are accumulated within
■ When the neuron fires, these ions swap locations via facilitated diffusion via
sodium and potassium channels
Sodium-Potassium Pump
An integral protein that exchanges 3 sodium ions (moves out of cell) with two potassium
ions (moves into cell)
The process of ion exchange against the gradient is energy-dependent and involves a
number of key steps:
1. Three sodium ions bind to intracellular sites on the sodium-potassium pump
2. A phosphate group is transferred to the pump via the hydrolysis of ATP
3. The pump undergoes a conformational change, translocating sodium across the
membrane
4. The conformational change exposes two potassium binding sites on the
extracellular surface of the pump
5. The phosphate group is released which causes the pump to return to its original
conformation
6. This translocates the potassium across the membrane, completing the ion
exchange
Steps Involved in Ion Exchange via a Sodium-Potassium Pump
Types of Membrane Transport
The membrane is principally held together by weak hydrophobic associations
between the fatty acid tails of phospholipids
This weak association allows for membrane fluidity and flexibility, as the
phospholipids can move around to some extent
This allows for the spontaneous breaking and reforming of the bilayer, allowing
larger materials to enter or leave the cell without having to cross the membrane
(this is an active process and requires ATP hydrolysis)
Endocytosis:
The fluidity of membranes allows materials to be taken into cells by endocytosis
It is the process by which large substances (or bulk amounts of smaller substances)
enter the cell without crossing the membrane
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An invagination of the membrane forms a flask-like depression which envelopes
the extracellular material
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The invagination is then sealed off to form an intracellular vesicle containing the
material
There are two main types of endocytosis:
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Phagocytosis – The process by which solid substances are ingested (usually to
be transported to the lysosome)
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Pinocytosis – The process by which liquids / dissolved substances are ingested
(allows faster entry than via protein channels)
Exocytosis
The process by which large substances (or bulk amounts of small substances)
exit the cell without crossing the membrane
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Vesicles (typically derived from the Golgi) fuse with the plasma membrane,
expelling their contents into the extracellular environment
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The process of exocytosis adds vesicular phospholipids to the cell
membrane, replacing those lost when vesicles are formed via endocytosis
Process of Exocytosis
Passive methods of transport across membranes
Simple diffusion
Simple diffusion occurs in a gas or liquid medium and only requires a concentration gradient.
Simple diffusion across membranes involves particles passing between the phospholipids in
the membrane. It can only happen if the phospholipid bilayer is permeable to the particles.
Non-polar particles such as oxygen can diffuse through easily.
Diffusion is the net movement of molecules from a region of high concentration to a
region of low concentration
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This directional movement along a gradient is passive and will continue until
molecules become evenly dispersed (equilibrium)
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Small and non-polar (lipophilic) molecules will be able to freely diffuse across cell
membranes (e.g. O2, CO2, glycerol)
The rate of diffusion can be influenced by a number of factors, including:
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Temperature (affects kinetic energy of particles in solution)
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Molecular size (larger particles are subjected to greater resistance within a fluid
medium)
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Steepness of gradient (rate of diffusion will be greater with a higher
concentration gradient)
Facilitated diffusion
Ions and particles that cannot diffuse between phospholipids can pass into or out of cells if
there are channels for them through the plasma membrane. Because these channels help
particles to pass through the membrane, from a higher concentration to a lower concentration,
the process is called facilitated diffusion.
Facilitated diffusion is the passive movement of molecules across the cell membrane
via the aid of a membrane protein
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It is utilised by molecules that are unable to freely cross the phospholipid bilayer
(e.g. large, polar molecules and ions)
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This process is mediated by two distinct types of transport proteins – channel
proteins and carrier proteins
Carrier Proteins
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Integral glycoproteins which bind a solute and undergo a conformational change
to translocate the solute across the membrane
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Carrier proteins will only bind a specific molecule via an attachment similar to an
enzyme-substrate interaction
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Carrier proteins may move molecules against concentration gradients in the
presence of ATP (i.e. are used in active transport)
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Carrier proteins have a much slower rate of transport than channel proteins (by
an order of ~1,000 molecules per second)
Channel Proteins
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Integral lipoproteins which contain a pore via which ions may cross from one
side of the membrane to the other
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Channel proteins are ion-selective and may be gated to regulate the passage of
ions in response to certain stimuli
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Channel proteins only move molecules along a concentration gradient (i.e. are
not used in active transport)
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Channel proteins have a much faster rate of transport than carrier proteins
Channel Proteins versus Carrier Proteins
The axons of nerve cells transmit electrical impulses by translocating ions to create a
voltage difference across the membrane
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At rest, the sodium-potassium pump expels sodium ions from the nerve cell,
while potassium ions are accumulated within
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When the neuron fires, these ions swap locations via facilitated diffusion via
sodium and potassium channels
Potassium Channels
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Integral proteins with a hydrophilic inner pore via which potassium ions may be
transported
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The channel is comprised of four transmembrane subunits, while the inner pore
contains a selectivity filter at its narrowest region that restricts passage of
alternative ions
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Potassium channels are typically voltage-gated and cycle between an opened
and closed conformation depending on the transmembrane voltage
Voltage-Gated Ion Channels
Osmosis
Water is able to move in and out of most cells freely. This net movement is osmosis.
Osmosis is the net movement of water molecules across a semi-permeable
membrane from a region of low solute concentration to a region of high solute
concentration (until equilibrium is reached)
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Water is considered the universal solvent – it will associate with, and
dissolve, polar or charged molecules (solutes)
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Because solutes cannot cross a cell membrane unaided, water will move to
equalise the two solutions
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At a higher solute concentration there are less free water molecules in
solution as water is associated with the solute
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Osmosis is essentially the diffusion of free water molecules and hence
occurs from regions of low solute concentration
Osmolarity refers to the concentration of a solution in terms of moles of solutes per litre of
solution.
Osmolarity is a measure of solute concentration, as defined by the number of osmoles
of a solute per litre of solution (osmol/L)
Solutions may be loosely categorised as hypertonic, hypotonic or isotonic according to
their relative osmolarity
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Solutions with a relatively higher osmolarity are categorised as hypertonic (high
solute concentration ⇒ gains water)
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Solutions with a relatively lower osmolarity are categorised as hypotonic (low
solute concentration ⇒ loses water)
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Solutions that have the same osmolarity are categorised as isotonic (same
solute concentration ⇒ no net water flow)
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Estimating Osmolarity
The osmolarity of a tissue may be interpolated by bathing the sample in solutions with
known osmolarities
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The tissue will lose water when placed in hypertonic solutions and gain water
when placed in hypotonic solutions
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Water loss or gain may be determined by weighing the sample before and after
bathing in solution
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Tissue osmolarity may be inferred by identifying the concentration of solution at
which there is no weight change (i.e. isotonic)
Tissues or organs to be used in medical procedures must be kept in solution to prevent
cellular dessication
This solution must share the same osmolarity as the tissue / organ (i.e. isotonic) in
order to prevent osmosis from occurring
Uncontrolled osmosis will have negative effects with regards to cell viability:
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In hypertonic solutions, water will leave the cell causing it to shrivel (crenation)
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In hypotonic solutions, water will enter the cell causing it to swell and potentially
burst (lysis)
In plant tissues, the effects of uncontrolled osmosis are moderated by the presence of
an inflexible cell wall
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In hypertonic solutions, the cytoplasm will shrink (plasmolysis) but the cell wall
will maintain a structured shape
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In hypotonic solutions, the cytoplasm will expand but be unable to rupture within
the constraints of the cell wall (turgor)
Summary of the Effects of Solute Concentrations on Cells
Vesicular Transport
Materials destined for secretion are transported around the cell in membranous
containers called vesicles
Endoplasmic Reticulum
The endoplasmic reticulum is a membranous network that is responsible for
synthesising secretory materials
Rough ER is embedded with ribosomes and synthesises proteins destined for
extracellular use
■ Smooth ER is involved in lipid synthesis and also plays a role in carbohydrate
metabolism
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Materials are transported from the ER when the membrane bulges and then buds to
create a vesicle surrounding the material
Golgi Apparatus
The vesicle is then transported to the Golgi apparatus and fuses to the internal (cis)
face of the complex
Materials move via vesicles from the internal cis face of the Golgi to the
externally oriented trans face
■ While within the Golgi apparatus, materials may be structurally modified (e.g.
truncated, glycosylated, etc.)
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Material sorted within the Golgi apparatus will either be secreted externally or may be
transported to the lysosome
Plasma Membrane
Vesicles containing materials destined for extracellular use will be transported to the
plasma membrane
The vesicle will fuse with the cell membrane and its materials will be expelled into the
extracellular fluid
Materials sorted by the Golgi apparatus may be either:
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Released immediately into the extracellular fluid (constitutive secretion)
Stored within an intracellular vesicle for a delayed release in response to a
cellular signal (regulatory secretion)
Overview of Vesicular Transport
Cell Origins
The theory that living cells arose from non-living matter is known as abiogenesis
This process is theorised to have occurred over four key stages:
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There was non-living synthesis of simple organic molecules (from primordial
inorganic molecules)
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These simple organic molecules became assembled into more complex
polymers
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Certain polymers formed the capacity to self-replicate (enabling inheritance)
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These molecules became packaged into membranes with an internal chemistry
different from their surroundings (protobionts)
Biogenesis
Miller-Urey Experiment
The non-living synthesis of simple organic molecules has been demonstrated by the
Miller-Urey experiment
Stanley Miller and Harold Urey recreated the postulated/recreated the conditions of
early pre-biotic Earth in a closed system by including a reducing atmosphere (low
oxygen) with high radiation levels, high temperatures and electrical storms in a closed
system of flasks and tubes. After running the experiment for a week, some simple
amino acids and complex oily hydrocarbons were found in the reaction mixture. This
experiment proved that the non-living synthesis of simple organic molecules was
possible.
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Water was boiled to vapour to reflect the high temperatures common to Earth’s
original conditions
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The vapour was mixed with a variety of gases (including H2, CH4, NH3) to create
a reducing atmosphere (no oxygen)
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This mixture was then exposed to an electrical discharge (simulating the effects
of lightning as an energy source for reactions)
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The mixture was then allowed to cool (concentrating components) and left for a
period of ~1 week
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After this time, the condensed mixture was analysed and found to contain traces
of simple organic molecules
Overview of the Miller-Urey Experiment
The chemical processes that contributed to the initial formation of biological life required
specific conditions to proceed
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This included a reducing atmosphere and high temperatures (>100ºC) or
electrical discharges to catalyse chemical reactions
These conditions do not commonly exist on modern Earth and hence living cells cannot
arise independently by abiogenesis
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Instead, cells can only be formed by the division of pre-existing cells (biogenesis)
Biogenesis describes the principle that living things only arise from other living things by
reproduction (not spontaneous generation)
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"Omne vivum ex vivo” – All life (is) from life
The law of biogenesis is largely attributed to Louis Pasteur, who demonstrated that
emergent bacterial growth in nutrient broths was due to contamination by pre-existing
cells
Broths were stored in vessels that contained long tubings (swan neck ducts) that
did not allow external dust particles to pass
■ The broths were boiled to kill any micro-organisms present in the growth medium
(sterilisation)
■ Growth only occurred in the broth if the flask was broken open, exposing the
contents to contaminants from the outside
■ From this it was concluded that emergent bacterial growth came from external
contaminants and did not spontaneously occur
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Overview of Pasteur’s Experiment into Biogenesis
Endosymbiosis
The theory of endosymbiosis helps to explain the evolution of eukaryotic cells. It states that
mitochondria were once free-living prokaryotic organisms that had developed the process of
aerobic cellular respiration. Larger prokaryotes that could only respire anaerobically took them
in by endocytosis. They allowed them to live in their cytoplasm. As long as the smaller
prokaryotes grew and divided as fast as the larger ones, they could persist indefinitely inside the
larger cells. The cells evolved to develop a mutualistic relationship turning it into a eukaryote
with membrane-bound organelles. In plant cells, the same thing happened with chloroplasts. If a
prokaryote that had developed photosynthesis was taken in by a larger cell and was allowed to
survive, grow and divide, it could have developed into the chloroplasts of photosynthetic
eukaryotes.
An endosymbiont is a cell which lives inside another cell with mutual benefit
Eukaryotic cells are believed to have evolved from early prokaryotes that were engulfed
by phagocytosis
The engulfed prokaryotic cell remained undigested as it contributed new functionality to
the engulfing cell (e.g. photosynthesis)
Over generations, the engulfed cell lost some of its independent utility and became a
supplemental organelle
Overview of the Process of Endosymbiosis
Evidence for Endosymbiosis
Mitochondria and chloroplasts are both organelles suggested to have arisen via
endosymbiosis
Evidence that supports the extracellular origins of these organelles can be seen by
looking at certain key features:
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Membranes (double membrane bound)
Antibiotics (susceptibility)
Division (mode of replication)
DNA (presence and structural composition)
Ribosomes (size)
Chloroplast and Mitochondrial Evidence
Cell Division
Cell cycle
The cell cycle is an ordered set of events which culminates in the division of a cell into
two daughter cells
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It can be roughly divided into two main phases:
Interphase
The stage in the development of a cell between two successive divisions
This phase of the cell cycle is a continuum of three distinct stages:
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G1 – First intermediate gap stage in which the cell grows and prepares for DNA
replication
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S – Synthesis stage in which DNA is replicated
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G2 – Second intermediate gap stage in which the cell finishes growing and
prepares for cell division
Interphase:
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DNA is present as uncondensed chromatin (not visible under microscope)
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DNA is contained within a clearly defined nucleus
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Centrosomes and other organelles have been duplicated
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Cell is enlarged in preparation for division
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M phase
The period of the cell cycle in which the cell and contents divide to create two
genetically identical daughter cells
This phase is comprised of two distinct stages:
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Mitosis – Nuclear division, whereby DNA (as condensed chromosomes) is
separated into two identical nuclei
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Cytokinesis – Cytoplasmic division, whereby cellular contents are segregated
and the cell splits into two
Cyclins
Mechanism of Cyclin Action
Cyclins are a family of regulatory proteins that control the progression of the cell cycle
Cyclins activate cyclin dependent kinases (CDKs), which control cell cycle processes
through phosphorylation
When a cyclin and CDK form a complex, the complex will bind to a target protein
and modify it via phosphorylation
■ The phosphorylated target protein will trigger some specific event within the cell
cycle (e.g. centrosome duplication, etc.)
■ After the event has occurred, the cyclin is degraded and the CDK is rendered
inactive again
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Cyclin Expression Patterns
Cyclin concentrations need to be tightly regulated in order to ensure the cell cycle
progresses in a proper sequence
Different cyclins specifically bind to, and activate, different classes of cyclin
dependent kinases
■ Cyclin levels will peak when their target protein is required for function and
remain at lower levels at all other times
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Mitosis
Mitosis is the process of nuclear division, whereby duplicated DNA molecules are
arranged into two separate nuclei
Mitosis is preceded by interphase and is divided into four distinct stages: prophase,
metaphase, anaphase, telophase
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The division of the cell in two (cytokinesis) occurs concurrently with the final
stage of mitosis (telophase)
Stages of Mitosis
Prophase:
DNA supercoils and chromosomes condense (becoming visible under
microscope)
■ Chromosomes are comprised of genetically identical sister chromatids (joined at
a centromere)
■ Paired centrosomes move to the opposite poles of the cell and form microtubule
spindle fibres
■ The nuclear membrane breaks down and the nucleus dissolves
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Metaphase:
Microtubule spindle fibres from both centrosomes connect to the centromere of
each chromosome
■ Microtubule depolymerisation causes spindle fibres to shorten in length and
contract
■ This causes chromosomes to align along the centre of the cell (equatorial plane
or metaphase plate)
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Anaphase:
Continued contraction of the spindle fibres causes genetically identical sister
chromatids to separate
■ Once the chromatids separate, they are each considered an individual
chromosome in their own right
■ The genetically identical chromosomes move to the opposite poles of the cell
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Telophase:
Once the two chromosome sets arrive at the poles, spindle fibres dissolve
■ Chromosomes decondense (no longer visible under light microscope)
■ Nuclear membranes reform around each chromosome set
■ Cytokinesis occurs concurrently, splitting the cell into two
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Cytokinesis
It is the division of the parental cytoplasm between the two daughter cells after mitosis (though
it often starts in telophase).
Cytokinesis is the process of cytoplasmic division, whereby the cell splits into two
identical daughter cells
Cytokinesis occurs concurrently with the final stage of mitosis (telophase) and is
different in plant and animal cells
Animal Cells
After anaphase, microtubule filaments form a concentric ring around the centre of
the cell
■ The microfilaments constrict to form a cleavage furrow, which deepens from the
periphery towards the centre
■ When the furrow meets in the centre, the cell becomes completely pinched off
and two cells are formed
■ Because this separation occurs from the outside and moves towards the centre,
it is described as centripetal
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Plant Cells
After anaphase, carbohydrate-rich vesicles form in a row at the centre of the cell
(equatorial plane)
■ The vesicles fuse together and an early cell plate begins to form within the
middle of the cell
■ The cell plate extends outwards and fuses with the cell wall, dividing the cell into
two distinct daughter cells
■ Because this separation originates in the centre and moves laterally, it is
described as centrifugal
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The mitotic index is a measure of the proliferation status of a cell population (i.e. the
proportion of dividing cells)
The mitotic index may be elevated during processes that promote division, such as
normal growth or cellular repair
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It also functions as an important prognostic tool for predicting the response of
cancer cells to chemotherapy
Identifying Mitotic Cells
Cells undergoing mitosis will lack a clearly defined nucleus and possess visibly
condensed chromosomes
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Prophase – Chromosomes condensed but still confined to a nuclear region
Metaphase – Chromosomes aligned along the equator of the cell
Anaphase – Two distinct clusters of chromosomes apparent at poles of the cell
Telophase – Two nuclear regions present within a single cell (difficult to see as
cytokinesis occurs concurrently)
Calculating Mitotic Index
The mitotic index is the ratio between the number of cells in mitosis and the total
number of cells
It can be determined by analysing micrographs and counting the relative number of
mitotic cells versus non-dividing cells
Cancers
Tumours are abnormal cell growths resulting from uncontrolled cell division and can
occur in any tissue or organ
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Diseases caused by the growth of tumours are collectively known as cancers
Mutagens
A mutagen is an agent that changes the genetic material of an organism (either acts on
the DNA or the replicative machinery)
Mutagens may be physical, chemical or biological in origin:
Physical – Sources of radiation including X-rays (ionising), ultraviolet (UV) light
and radioactive decay
■ Chemical – DNA interacting substances including reactive oxygen species (ROS)
and metals (e.g. arsenic)
■ Biological – Viruses, certain bacteria and mobile genetic elements (transposons)
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Mutagens that lead to the formation of cancer are further classified as carcinogens
Oncogenes
An oncogene is a gene that has the potential to cause cancer
Most cancers are caused by mutations to two basic classes of genes –
proto-oncogenes and tumour suppressor genes
Proto-oncogenes code for proteins that stimulate the cell cycle and promote cell
growth and proliferation
■ Tumour suppressor genes code for proteins that repress cell cycle progression
and promote apoptosis
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When a proto-oncogene is mutated or subjected to increased expression it becomes a
cancer-causing oncogene
Tumour suppressor genes are sometimes referred to as anti-oncogenes, as their normal
function prevents cancer
Relationship between Proto-Oncogenes and Tumour Suppressor Genes
Metastasis
Tumour cells may either remain in their original location (benign) or spread and invade
neighbouring tissue (malignant)
Metastasis is the spread of cancer from one location (primary tumour) to another,
forming a secondary tumour
Secondary tumours are made up of the same type of cell as the primary tumour – this
affects the type of treatment required
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E.g. If breast cancer spread to the liver, the patient has secondary breast cancer
of the liver (treat with breast cancer drugs)
Formation of Secondary Tumours via Metastasis