Cell Organisation

& Communication
Oct 2022
Dr Jason Chu
j.chu@mmu.ac.uk
Teaching Approach (And Why?)
• Lecture – provide you with content
• Interactivity – active learning, engagement, collaboration, opportunity to make mistakes
• Quizzes – via Mentimeter or Vevox, to improve recall
ILOs
• Explain how molecules are transported across membranes
• Summarise how cells form tissues
• Compare and review the terms local and distant signalling
• Describe the three main stages of signalling process
• Summarise how defects in cell signalling can cause disease
What do you know about this topic?

https://manmetuni.padlet.org/jasonchu/communication
Membrane Transport
Diffusion
Simple Diffusion – unassisted movement down the gradient
• Most straightforward route for solute to cross
membrane.
• Unassisted net movement from high to low
concentration.
• Typically only possible for gases, non-polar
molecules or small polar molecules e.g. water,
glycerol or ethanol. (a) Diffusion of one solute

Molecule with asymmetrical charges

(b) Diffusion of two solutes

Osmosis Permeable to water but not solutes
• If two solutions are separated by a selectively
permeable membrane, the water will move towards
the region of higher solute concentration
• For most cells, water tends to move inwards (region of
higher solute concentration)
• Water balance of cells:
• Isotonic solution – solute concentration is the same
as that inside the cell; no net water movement
• Hypertonic solution – solute concentration is
greater than that inside the cell; cell loses water
• Hypotonic solution – solute concentration is less
than that inside the cell; cell gains water
Facilitated Diffusion – Protein-mediated movement down the gradient
• Most substances are too large or too polar to cross membranes
by simple diffusion
• These need the assistance of transport proteins Channel protein
• Transport proteins are large, integral membrane proteins with
multiple transmembrane segments
• Channel proteins form hydrophilic channels through the membrane
to provide a passage route for solutes
• Carrier proteins bind solute molecules on one side of a membrane,
undergo conformational change, and release solute on the other side
of the membrane

Carrier protein
Channel proteins
• Hydrophilic channel through the phospholipid bilayer [solute] HIGH

• Passage for solutes

• Aquaporins
• Movement of water across cell membranes in some
tissue was faster than expected given polarity of water
molecule
• Aquaporin (AQP) allows rapid passage of water through [solute] LOW
membranes of erythrocytes and kidney cells.
• Ion Channels
• Allow diffusion of ions e.g. K+ and Na+
• Most ion channels are gated, and need a stimuli to open The stable voltage across membrane
• Often maintain the resting membrane potential of cell
Ion Channels - gating
Carrier proteins
• Undergo subtle change in shape that translocate the solute-
binding site across the membrane
• This conformational change is triggered by binding or release
of the solute
[solute] HIGH
• Facilitated diffusion is still passive
Solute moves down the concertation gradient
No energy required

• Transport proteins can move solutes against the [solute] LOW

concentration gradient
Active transport requires energy
Active transport
• Moves substances against concentration gradient
• Requires energy – usually ATP
• Often by specific proteins embedded in the membrane
• Allows cells to maintain concentration gradient that differ from their surroundings
E.g. sodium-potassium pump
Sodium-potassium pump

1 2
Cytoplasmic Na+ binds to Na+ binding stimulates
sodium-potassium pump. phosphorylation by ATP
Affinity for Na+ is high when
the protein is in this shape
Sodium-potassium pump

3 4
The new shape has a high
Phosphorylation leads to
affinity for K+, which binds on
change in protein shape,
the extracellular side and
reducing its affinity for Na+,
triggers the release of the
which is released outside
phosphate group
Sodium-potassium pump

5 6
Loss of the phosphate group
K+ is released; affinity for Na+
restores the protein’s original
is high again, and the cycle
shape, which has a lower
repeats
affinity for K+
Co-transport
• When the active transport of a solute indirectly drives the transport of other substances
• E.g. Sucrose-H+ co-transporter

symport

antiport
Cell Case Study Example

Erythrocyte (RBC) plasma membrane transport mechanism

• The membrane potential maintained by active transport of potassium [K+] ions inwards and
sodium [Na+] ions outwards.
• Specialised pores or channels allow water and ions to enter or leave cell rapidly.
Cell Case Study Example

Find another cell type

• Summarise the types of transport and channels it has
Bulk transport
• Large molecules (e.g. polysaccharides and proteins) cross the
membrane in bulk via vesicles
• This requires energy
• Exocytosis – transport from within the cell to be released outside
• Membrane bound vesicles buds from the Golgi apparatus
and moves along microtubules to the plasma membrane
• Vesicle fuses with the plasma membrane and expel its
contents to the extracellular space
• Endocytosis – transport of macromolecules into cell
• Reversal of exocytosis. There are three main types:
1. Phagocytosis “cellular eating”
2. Pinocytosis “cellular drinking”
3. Receptor-mediated endocytosis
 https://manmetuni.padlet.org/jasonchu/3MTsucrose

3 Minute Thesis
What might happen to a cell if it is put into a sucrose
concentrated solution? (3 marks)
• Uptake of sucrose into cell (high to low concentration)
• Co-transport – sucrose and H+ ions (then active H+ protein pump out)
• Hypertonic – cell loses water and shrinks
Cell Organisation
Organising cells into tissue
• There are over 200 different cell types in the body:
Name as many as you can think?

• Four major tissue types:

1. Epithelial Tissue
2. Connective Tissue
3. Muscular Tissue
4. Nervous Tissue
Organising cells into tissue
1. Epithelial Tissue
• Covers the outside of the body and lines the organs
and cavities within the body
• Contains cells that are closely joined into multicellular
sheets
• Is avascular Absent of blood vessels

• Polarised cellular structure

• Free apical – can be specialised
• Microvilli (actin)
• Cilia (microtubules)
• Basolateral membrane adhesions
1. Epithelial Tissue
Terminology
• Simple = single layer of cells
• Stratified = multiple layers of cells
• Pseudostratified = single layer of varying length

Shape
• Squamous (like floor tiles)
• Cuboidal (like dice)
• Columnar (like upright bricks)
Squamous Epithelia What shape is this?
• Simple squamous epithelium Draw it out
• Absorption and diffusion

• Mesothelium
• Lines body cavities
• Endothelium
• Forms inner lining of heart and blood vessels
Cuboidal Epithelial
• Simple cuboidal epithelium

• Stratified cuboidal epithelium

Columnar Epithelia
• Simple columnar epithelium
• Absorption & secretion
• E.g. stomach, small intestine, large intestine
Columnar Epithelia
• Pseudostratified columnar epithelium
• Typically have cilia
• Found in nasal cavity, trachea, bronchi
Columnar Epithelia
The part of the throat behind the mouth and nasal cavity
• Stratified columnar epithelium
• Relatively rare
• Provide protection in pharynx, anus, urethra
Glandular Epithelia – collection of epithelial cells that produce secretions
Two types of glands

1. Endocrine glands:
Release hormones that directly enter bloodstream
e.g. pituitary, thyroid, hypothalamus and adrenal

2. Exocrine glands:
Produce and secrete substances which then travel through ducts
onto epithelial surfaces
e.g. sweat, salivary, mammary, sebaceous, prostate and mucous
2. Connective Tissue
• Connects epithelium to rest of body
• Abundance of extracellular matrix (ECM)
• Various properties:
• Tough & flexible e.g. tendons Transparent, colourless gel-like substance
• Shock absorbing e.g. cartilage
• Hard & dense e.g. bone
• Soft & transparent e.g. vitreous humour of eyeball

• Collagen is key
Makes up 25% of total protein mass in mammals
2. Connective Tissue
Types:
• Connective Tissue Proper
• Loose – Adipose
• Dense – Tendons

• Fluid connective tissues

• Blood & Lymph

• Supporting connective tissues

• Cartilage & Bone
Connective Tissue Fibres
• Collagen Fibres
• Rope like fibrous proteins
• Strong & flexible
• Tendons made of collagen

• Reticular Fibres
• Form branch like networks
• Offer support and stability to organs
• Supporting mesh in liver and bone marrow

• Elastic Fibres
• Interconnect structures like vertebrae
• Branched elastic fibres that stretch and return to their original shape
• Contain protein elastin
• Allows arteries and veins to be elastic and resilient
Connective tissue cells
• Fibroblasts (synthesis of ECM, wound healing)
• Osteoblasts (bone synthesis)

• Adipose cells (Fat)

• Macrophages (phagocytosis)
• Mast cells (inflammation)
• Lymphocytes (immunity)
• Other blood cells –monocytes, eosinophils, basophils, neutrophils
3. Muscular Tissue
Specialised for contraction

Three types of muscle tissue:

1. Skeletal muscle
Large muscles responsible for body movement
2. Cardiac muscle
Only found in the heart
3. Smooth muscle
Found in walls of hollow, contracting organs
4. Nervous Tissue

Specialised for conducting electrical impulses

Concentrated in brain and spinal cord

Types of cells in nervous tissue

• Neurons
• Neuroglia (supporting cells)
Organs
Will be composed of multiple tissue types (made of different cells).

Stomach (as an example)

• Lining, transport, secretion,

absorption Epithelial

• Support strength & elasticity Connective

• Movement
Muscle
• Information synthesis,
communication, control Nervous
Organs
Will be composed of multiple tissue types (made of different cells).

Another organ?

Epithelial

Connective

Muscle

Nervous
Match the cell type/tissue to its function
Match the correct cell type/tissue to its role in the body

1. Adipocytes a) Protection
2. Goblet cells b) Protection
3. Simple squamous c) Secretion/absorption
epithelium d) Absorption
4. Stratified epithelium e) Store fat
5. Columnar epithelium f) Movement
6. Villi g) Secrete mucous
7. Keratin h) Passive diffusion
8. Cilia
Match the cell type/tissue to its function
Match the correct cell type/tissue to its role in the body

1. Adipocytes a) Protection
2. Goblet cells b) Protection
3. Simple squamous c) Secretion/absorption
epithelium d) Absorption
4. Stratified epithelium e) Store fat
5. Columnar epithelium f) Movement
6. Villi g) Secrete mucous
7. Keratin h) Passive diffusion
8. Cilia
Cell signalling
Cellular signalling
• Essential communication between cells and the environment
• Signals are often chemicals
• Can be local or long distance

umwelt
Local vs Long-distance Cellular Signalling

• How does communication occur?

• What chemicals or messenger molecules do they use?

• What are the three stages of cellular signalling?

https://manmetuni.padlet.org/jasonchu/cellularsignalling
Local cellular signalling
• Can be via direct contact
• Human cells have cell junctions that connect
cytoplasm of adjacent cells
• Communication can also occur through cell-surface
molecules
• Paracrine signalling
• Secreted messenger molecules that travel short
distances
• Can be growth factors or cytokines
• Synaptic signalling
• When electrical activity triggers the release of a
neurotransmitter
• This diffuses across a narrow space called
synapse and stimulates a target cell
Long-distance cellular signalling
• Animal cells use chemicals called hormones – endocrine signalling
• Specialised cells produce and release hormones, which travel via circulatory system
• Cells need specific receptors to respond to according hormones

Endocrine cell

Target cell
specifically
binds hormone
Hormone travels
in bloodstream
Blood
vessel
Endocrine vs Nervous
Three stages of cellular signalling

1. Reception
• A chemical signal binds to a cellular protein
• The cellular protein is typically on the cell surface or inside the cell

2. Transduction
• Binding of the signal leads to a change in the receptor

3. Response
• The transduced signal triggers a specific cellular activity
Three stages of cellular signalling

1 Reception 2 Transduction 3 Response

Receptor
Activation of
cellular
response
Relay molecules
Signalling
molecule
1.1 Reception

• Binding between signal molecule (ligand) and receptor is highly specific

• Ligand binding causes receptor protein to undergo change in shape, this

is often the initial transduction of the signal

• Most signal receptors are plasma membrane proteins and there are
three main types:
1. G protein-coupled receptors (GPCR)
2. Receptor tyrosine kinases (RTK)
3. Ion channel receptors
 Signalling molecule
G protein-couple receptors binding site

• GPCRs are the largest family of cell-surface receptors

• Consists of a 7 α-helix domain protein that associates with G protein
• They bind to various signalling molecules e.g. epinephrine and neurotransmitters
Signalling
molecule Segment that
interacts with
inactive
Activated G proteins
GPCR Enzyme
GPCR
GTP
GDP GDP
G protein GTP
GDP
(inactive) Enzyme

activated
Enzyme
GTP
GDP

Pi

Cellular
response
Receptor tyrosine kinases
• RTKs are membrane bound receptors that
attach phosphates to tyrosine Signalling molecule
(ligand) Ligand-binding
• One RTK can trigger multiple signal site

transduction pathways at once

• Can help the cell regulate many coordinated Tyrosines
cellular responses e.g. growth & reproduction
RTK proteins Dimer
(inactive monomers)
Fully activated RTK
• Abnormal RTK function is associated with Activated dimer (phosphorylated dimer)
many cancers
Cellular
response 1
Cellular
ATP
• RTKs transfer phosphate from ATP (creating ADP response 2

ADP) to target protein

Phosphorylated Activated relay
• RTKs span the membrane and have a tyrosine proteins
Inactive relay proteins
intracellular tail with several tyrosines
Ion Channels
• Allows diffusion of ions (e.g. K+ and Na+) through a pore
• Most ion channels are gated, and will only open following a
stimuli
• Often maintains the resting membrane potential of the cell

Ligand gated ion channels

• Gate will only open when a specific ligand binds
• Receptor will then change shape and allow flow
• The change in ion concentration can affect activity of cell
Intracellular receptors

• Intracellular receptors are found in the cytoplasm or nucleus

of target cells

• Small or hydrophobic chemical messengers can readily cross

the membrane and activate these receptors
e.g. Steroid or thyroid hormones
An activated hormone-receptor complex can act as a
transcription factor, and turn on specific genes
What’s the difference between GPCR and RTK?

https://manmetuni.padlet.org/jasonchu/GPCRRTK
 2 Signal transduction
• Many of the conformational changes that occur during signal transduction are brough about by
phosphorylation
• Another group of signalling molecules are known as second messengers:
• Cyclic AMP
• G proteins
• Calcium ions (Ca2+)
Protein phosphorylation
• Phosphorylation and dephosphorylation are widespread cellular mechanisms
• Protein kinases transfer phosphates from ATP to protein
• There are many relay molecules in signal transduction, creating a
phosphorylation cascade
• Kinase enzymes add phosphates and phosphatases remove phosphates
• This system acts as a molecular switch to turn on and off activities as required

Inactive
protein kinase
1 Active
protein
kinase 1 Inactive
protein kinase ATP
Inactive 3 ADP P
protein kinase ATP Active
2 ADP P protein
Active PP kinase 3
protein Pi
PP kinase 2
Pi
Inactive
Inactive
ATP
protein ATP
protein kinase P
3 P ADP
Active Active Cellular
protein
PP kinase 3 PP protein response
Pi Pi
Second Messengers
• They are small, non-protein, water-soluble molecules or ions that
spread throughout the cell by diffusion
• They participate in pathways initiated by GPCRs and RTKs
e.g. Cyclic AMP (cAMP) and calcium ions

cAMP
• An activated G protein binds adenylyl cyclase, an enzyme in the plasma
membrane that converts ATP to cAMP
• cAMP diffuses through the cell and activates protein kinase A

Calcium ions
• Its concentration in the cytoplasm is normally lower than outside the cell
• Increase in Ca2+ may cause: contraction of muscle cells; secretion of
substances; cell division
Phosphorylation enzymes:
What adds phosphates?
What removes phosphates?
4.3 Response
• Signal transduction pathway can lead to regulation of one or more cellular activities
• The response may occur in the cytoplasm or in the nucleus
• Cytoplasmic responses are often the activation of enzymes or opening of ion channels
• Nuclear responses involve the synthesis of enzymes or other proteins, usually by turning genes
on or off in the nucleus.
• Activated receptors may act as transcription factors
4.3 Response
Signal Termination
• Inactivation mechanisms are just as vital
• For a cell to remain alert and capable of responding to incoming signals, each molecular change in
its signalling pathways must last only a short time
• If signalling pathway components become locked into one state, whether active or inactive, the
proper function of the cell can be disrupted
• Consider how this might be apparent in tumour cells
Summary
ILOs
• Explain how molecules are transported across membranes
• Summarise how cells form tissues
• Compare and review the terms local and distant signalling
• Describe the three main stages of signalling process
• Summarise how defects in cell signalling can cause disease
Summary
• Membrane Transport:
simple & facilitated diffusion; channel/carrier proteins, active transport
• Major Tissue types – Epithelial, Connective, Muscular, Nervous
• Cells → Tissues → Organs
• Local cellular signalling – paracrine & synaptic
• Long distance signalling – endocrine / hormones
• Stages of cellular signalling – Reception, Transduction, Response
R: GPCR, RTKs, Ion channels
T: Phosphorylation, second messengers
R: Enzyme activity or nuclear transcription factors
Programme Support Tutors (PSTs)
Office: JD E231 HCSPST@mmu.ac.uk

d.akhidime@mmu.ac.uk
Dr Jason Chu
r.parkhouse@mmu.ac.uk j.chu@mmu.ac.uk
What
questions do
you still have?
What is still
unclear?

https://manmetuni.padlet.org/jasonchu/questions