Cell Structure & Function of Cellular Organelles

LECTURES
COVERED
IN THIS
MODULE
2
Lecture 1:
• Cell Structure
Lecture 2:
• Function of Cellular Organelles

Lecture 1:
Learning
Outcome of
Cell Structure
• To understand basics of
molecular cell biology
• To recognize Principles of Cell
Theory
• To distinguish different cell types
and its fundamental functions
3

Lecture 2:
Learning
Outcome of
Function and
Biochemistry
of Cellular
Organelles
• To identify basic cellular function
and disease it could cause
• To understand how cells
communicate with one another
and integrate the organelles
functions within the cell
organization
• To understand adaptation of cells
to changing conditions
4

Why Do I Need to Learn This?
5

Why Do I Need to Learn This? 6
CREDIT:
KELLIE
HOLOSKI/SCIENCE
TRANSLATIONAL
MEDICINE

Molecular Cell Biology Concept Map
7

Relationship Between Molecular Biology,
Biochemistry & Genetics
• Molecular biology - interactions between the various
systems in a cell; inter-relationship of DNA, RNA &
protein synthesis and regulation.
8
Function
Genes
Proteins
Biochemistry
Molecular Biology
Genetics
Schematic relationship between Biochemistry, Genetics & Molecular Biology
Cell

Molecular
Biology
9
overlaps between genetics
& biochemistry.
study gene structure &
function at molecular
level.
allows the laboratory to be
predictive in nature; events
that occur in the future.

Why Cell Biology Is So Important?
• Patients with disease or disorder such as meningitis, malaria,
diabetes, cancer, cystic fibrosis, or Alzheimer’s disease, are caused
by problems at a cell or molecular level. Physical damage e.g. burn
or broken bone also causes damage at cell level.
• By understanding how cells work in healthy and diseased states,
cell biologists able to develop vaccines, effective & improved
qualities of medicines, produce ‘health forecast’ by analyzing
genetic database, that could be a way for a person to take
preventive measure.
• Assisted the human fertility programme, DNA testing has been
used in archaeology, forensic medicine, DNA fingerprinting in crime
investigation
• A basic understanding of cell biology including genetics will be as
important as having some knowledge about computers and
Internet, especially for those in medical line. 10

To Understand
The Basis For
Disease, It’s
Important To
Understand
Cell Biology
• Ageing (telomere shortening)
• Cancer (errors in cell division, migration,
cell polarity, growth, etc)
• Cystic fibrosis(misfolding of key protein
cause defect in calcium-ion channel)
• Congenital heart defects (errors in cell
migration during development)
• Food-borne illness (Salmonella, E. coli)
• Hypertension (defective cell-cell adhesion
in the kidney)
• Hypercholesterolemia (defective uptake of
lipoproteins)
• Lysosomal storage disease (defective
intracellular transport of enzymes)
• Muscular dystrophy (defective attachment
of plasma membrane to cytoskeleton)
11
All disease states are
caused at the cellular level

To Understand
The Basis For
Disease, It’s
Important To
Understand
Cell Biology
12

• Sickle-cell Disease
disease experience anaemia -
blood disorder - defects in
erythrocytes. Haemoglobin in red
blood cells is mutated, changes the
shape of the RBC to sickle shape
causing the cells ineffectively carry
O2. Require blood transfusions to
treat the disease.
• Alzheimer's Disease
develop harmful “protein plaques”
- disrupt neighbouring neurons
function, affecting neuron
structure to collapse, creating
neurofibrillary tangles that cause
neuron cell death. Progressive
neuron loss, cause AD patients to
suffer from dementia, memory
loss, defects in motor function,
personality and behavioral
changes.
13
To Understand
The Basis For
Disease, It’s
Important To
Understand
Cell Biology

3 Principles of Cell Theory
14
2. Basic units of life
(Smallest Functional Units
of structure in organisms)
3. Cells are produced by the division of
Preexisting Cells (This principle discarded
the idea of spontaneous generation
1. All living things are made of cells
(Building Blocks)

Additional (6) Cell’s Principles
1. Grow, Divide & Die INDEPENDENTLY (+,÷, -).
2. Has Structure, Function, Reproduction & Heredity.
3. Controlled by DNA
4. Genetic information is Stored & Expressed.
5. Uses Only A Part Of The Coded gene info, which is
Necessary For Its Specialized structure and function
6. Maintain it’s Homeostasis to remain alive
15

6 TEACHING
MESSAGES
All living things are made up of building
blocks called cells.
Teaching
Message 1:
(P1)
Cells are incredibly small –need
microscopes to see them.
Teaching
Message 2:
(P2)
All cells & its structures have the same
basic parts to do specific tasks
Teaching
Message 3:
(AP2&4)
Cells divide to grow and repair - Mitosis.
Teaching
Message 4:
(P3 & AP1)
Cells differentiate to become specialized
e.g., muscle cells, nerve cells blood cells
Teaching
Message 5:
(AP2,3&5)
Different cell types group together to form
organs systems, All systems work together to
form a living and functional organism.
Teaching
Message 6:
(P1,
AP2&6) 16

3 Basic Cell’s Characteristics
1. Plasma membrane – Phospholipids Bilayer
2. Cytoplasm – Cytosol + Organelles + Inclusions
Jelly-like substance outside nucleus &
inside plasma membrane
3. Genetic material – DNA
Protoplasm : Cytoplasm + Nucleoplasm
(eukaryotic only)”
A liquid - like sol @ a jelly - like gel 18

Cell Types
19
Basic Eukaryotic & Prokaryotic Differences
Eukaryote - membrane-enclosed DNA (nucleus) &
membrane-bound organelles.
Prokaryote - have no membrane-bound DNA (nucleoid) &
lacks other membrane-bound organelles.

Prokaryotic Cells
• Unicellular
• Genetic material - single
circular loop of naked single/
double-stranded DNA.
• Flagella & pili for (i)
Movement (ii) Rotary Motion
• 3 major shapes: rod, spherical
and spiral shaped.
• Mostly divide by Binary fission.
20

Origin Of A Eukaryotic Cell
21
 A prokaryotic host cell incorporates another prokaryotic cell.
 Each prokaryote has its own set of DNA molecules (a genome).
 The genome of the incorporated cell remains separate (curved blue line) from the host
cell genome (curved purple line).
 The incorporated cell may continue to replicate as it exists within the host cell.
 Over time, during errors of replication or perhaps when the incorporated cell lyses and
loses its membrane separation from the host, genetic material becomes separated from
the incorporated cell and merges with the host cell genome.
 Eventually, the host genome becomes a mixture of both genomes, and ultimately
enclosed in an endomembrane, a membrane within the cell that creates a separate
compartment.
 This compartment eventually evolves into a nucleus.
http://www.nature.com/scitable

 Mitochondria and chloroplasts likely evolved from engulfed bacteria that once lived as
independent organisms.
 At some point, a eukaryotic cell engulfed an aerobic bacterium, which then formed an
endosymbiotic relationship with the host eukaryote, gradually developing into a
mitochondrion.
 Eukaryotic cells containing mitochondria then engulfed photosynthetic bacteria, which
evolved to become specialized chloroplast organelles.
 http://www.nature.com/scitable
22
Origin Of Mitochondria And Chloroplasts

6 TEACHING
MESSAGES
All living things are made up of building
blocks called cells.
Teaching
Message 1:
(P1)
Cells are incredibly small –need
microscopes to see them.
Teaching
Message 2:
(P2)
All cells & its structures have the same
basic parts to do specific tasks
Teaching
Message 3:
(AP2)
Cells divide to grow and repair - Mitosis.
Teaching
Message 4:
(P3 & AP1)
Cells differentiate to become specialized
e.g., muscle cells, nerve cells blood cells
Teaching
Message 5:
(AP2 &
AP3)
Different cell types group together to form
organs systems, All systems work together to
form a living and functional organism.
Teaching
Message 6:
(P1 & AP2)
23

Teaching
Message 1:
All living
things are
made up of
building
blocks called
cells.
24

3 Germ Layers of
Embryonic Cell
25

Functions of Epithelia Cell
1. Protection : from Mechanical trauma, Dehydration, Pathogens
2. Secretion : Mucous & serous products cells
Hormones, milk, sweat Enzymes, HCl,
3. Lubrication : in GI tract, Fetus in birth canal, Joints
4. Transporter: Ion-transporting cells (wastes Filtration: Urine)
Kidney tubules, Gall bladder etc.)
5. Absorption : Amino acids, Glucose, Fatty acids
6. Reproduction: Germ cells
7. Neuroepithelium / Sensory: Detect stimuli e.g.Taste, Smell,
Hearing 26

Functions of Epithelia Cell
27

• Humans, plants,
animals, and
bacteria are made
up of cells.
• Where do cells are
located in our body?
• EVERYWHERE!!!
28

Teaching
Message 2:
Cells are
INCREDIBLY
SMALL –need
microscopes to
see them.
29
29
Scanning electron µscope (SEM) 3-D image
Fate of the SARS-CoV-2 particles adhered to the cell surface at 48 hpi. (A, B)
Cell membrane ruffles about to wrap several viral particles (arrows). Viruses
could also be observed on the edge of membrane ruffles (arrowheads) (A) and
phyllopodium-like extensions (B). In (C) a viral particle could be seen adhered
to the edge of the microvilli-like structure (arrow) next to membrane ruffles
(long arrow) surrounding SARS-CoV-2 particles (arrowheads). (D)
Communications between two infected cells are indicated with arrowheads.
One of the bridges between the cells was depicted in the rectangle. A higher
magnification of this area is shown in (E) and displays viral particles (arrows)
on their surface. Aggregates of SARS-CoV-2 particles
(arrowheads) were also observed on the surface of both cells.
MOI = 0.1; Bars: (A–C, E) 200 nm; (D) 1 µm.
Caldas, L.A., Carneiro, F.A., Higa, L.M. et al. Ultrastructural analysis of SARS-CoV-2
interactions with the host cell via high resolution scanning electron microscopy. Sci Rep
10, 16099 (2020). https://doi.org/10.1038/s41598-020-73162-5

Teaching
Message 2:
Cells are
INCREDIBLY
SMALL –need
microscopes to
see them.
30
30
Transmission electron µscope
(TEM) 2-D image
Sachet, M., Liang, Y. Y., & Oehler, R. (2017). The immune response to
secondary necrotic cells. Apoptosis : an international journal on programmed
cell death, 22(10), 1189–1204. https://doi.org/10.1007/s10495-017-1413-z

Cells Have Large Surface Area-to-Volume Ratio
31
Animation: “How big is a cell?”
http://www.cellsalive.com/howbig.htm
Watch the “Cell & Molecular Size” at
http://www.youtube.com/watch?v=l7kZjdeo0Cs

Teaching
Message 3:
All cells & Its
structures have
the same basic
parts to do
specific tasks
32
Biology: Cell Structure - YouTube
https://www.youtube.com/watch?v=URUJD5NEXC8

Cell Structure
1. Cell Wall
2. Plasma Membrane
3. Membrane Protein
4. Cell Junctions
5. Cytoplasm
6. Cytoskeleton
7. Cilia & Flagella 35
8. Centrioles
9. Nucleus
10. Endomembrane System (ES)
i. Endoplasmic Reticulum
ii. Golgi Apparatus
iii. Transport Vesicle
11. Mitochondria

1. Cell Wall (Mostly in Plant)
• Provides structure, support &
protection
• Connect by plasmodesmata
(channels through the walls)
• Found in plants, bacteria, fungi,
algae and some archaea.
• Animals and protozoa do not have
cell walls.
38

2. Plasma Membrane
• Provides Structural Integrity that holds cells together.
• Asymmetric
• Double layer of phospholipids & proteins
Each lipid molecule contains
(i) hydrophobic, “Water-fearing” @ nonpolar tail
(ii) hydrophilic , “Water-loving” @ polar head
• Cell Identity Markers - External surface,
 Glycolipids =
Carbohydrate groups + cholesterol + lipids
 Glycoproteins =
Carbohydrate groups + protein
39

2. Plasma Membrane -Functions
1. Form specialized Compartments By Selective Permeability via
Creation of concentration gradients, pH & charge
2. Membrane Fluidity – for endocytosis, exocytosis and membrane
biogenesis (synthesis of cell membrane in new cell growth)
3. Cell-Cell Recognition & Communicate through chemical
signaling and membrane junctions.
4. Site For Receptor molecule binding for cell signaling (e.g.
hormone)
5. Controls & Regulates reaction sequences - homeostasis
• Product of one enzyme is the substrate for the next enzyme
• Can "line up" the enzymes in the proper sequence
• Regulates water movement, nutrients, & wastes in the cell
41

42
plays an essential role in neural growth and repair but,
later in life, a corrupted form can destroy nerve cells, leading
to the loss of thought and memory in Alzheimer's disease.

43
Outside
Plasma
membrane
Inside
Transporter Cell surface
receptor
Enzyme
Cell surface identity
marker
Attachment to the
cytoskeleton
Cell adhesion/
anchor
3. Membrane Proteins

Genetic Diseases –
Cell Membrane
Some membrane Diseases are hereditary e.g
• CYSTIC FIBROSIS - recessive genetic disease -
both parents contribute 1 affected gene to the
child causing mutation in the cystic fibrosis
transmembrane conductance regulator (CFTR)
protein, which functions to move water and
salt across the cell membrane.
• In CF, cells do not secrete enough water, causes
the mucus to become dehydrated, extremely
thick, sticky that the cilia are unable to propel
mucus out of the lungs. Symptoms -
wheezing, persistent cough, breathing difficult
due to the build-up of mucus, cause germs to
grow, and prone for infection. CF can also cause
digestive problems, including lack of weight
gain, constipation, and intestinal blockage.
46

4. Cell Junctions: Junctional &
Non-Junctional Adhesion
48

1. Tight junctions
• See between stomach cells
2. Anchoring junctions –
• cytoskeleton fibers join cells in tissues that need to stretch
• Adherens junctions, Desmosomes & Hemidesmosomes - See between heart,
skin, and muscle cells
3. Gap junctions
• This links the cytoplasm of adjoining cells 49

51
Anoikis: Type Of Apoptosis For
Cells That Denied Adhesion

53
If you were expecting to find a high
degree of
1. flexibility between cells, what
type of junctions, would it be?
2. control over movement of
substance thru intercellular
spaces, what type of junctions,
would it be?
3. strong coordination of
information among
neighboring cells, what type of
junctions, would it be?
4. What moves through gap
junctions?
4. Cell Junctions

54
1. Anchoring junction (flexibility
between cells)
2. Tight junctions (act as barriers
that regulate the movement of
water and solutes between
epithelial layers) control over
movement of substance thru
intercellular spaces
3. Gap junctions (involved in
cellular communication) -
strong coordination of
information among
neighboring cells
4. Gap junctions allow direct
diffusion of ions and small
molecules between adjacent
cells.
4. Cell Junctions

5. Cytoplasm
• Cytoplasm –
Betweenthecellmembrane
andthenucleus
• Cytoplasm =
Cytosol + Organelles + Inclusions
55

Organelles
• Non-Membranous Organelles
• Cytoskeleton, Microvilli,
Centrioles, Cilia, Ribosomes,
Proteasomes
• Membranous Organelles
• Endoplasmic Reticulum, Golgi
Apparatus, Lysosomes,
Peroxisomes, Mitochondria
56

6. Cytoskeleton
Strength &
Flexibility
A Network Of Filaments & Tubules
that extends from nucleus to plasma
membrane Support Cell Shape &
Anchor Organelles.
58

• Tough supporting network / structural stability
• Distribute tensile forces across cell
INTERMEDIATE FILAMENTS
• Can be easily assembled and disassembled (centriole form spindle
during mitosis)
• Provide network & organization to the cell & move materials within
the cell (mitochondria movement)
MICROTUBULES
• Responsible for cell shape and motility;
• Provide energy for contractile crawling, “pinching” processes
MICROFILAMENTS / ACTIN FILAMENTS
59
6. Cytoskeleton – 3 Types

Tissue level:
 muscle movement– skeletal muscle
Cellular level:
 determines shape of the cell
 cells motility
 cell adhesion
 mitosis, meiosis
Subcellular level:
 anchors organelles
 organization of organelles
 provides mechanical/tensile strength
 movement of chromosomes
 organizing cell polarity
 Intracellular movement of vesicles
- Endocytosis – clathrin-mediated endocytosis and phagocytosis
6. Function Of The Cytoskeleton
Dynamic
Adaptable
Stable
Strong
Cell Adhesion Needs Cytoskeleton
60
No Affect on Cell
Cell Adhesion

Why do we care about cell locomotion?
1) Host defense
2) Angiogenesis
3) Wound healing
4) Cancer metastasis
5) Tissue engineering
Steps:
i. Protrusion
ii. Adhesion
iii. Traction
61
6. Cytoskeleton – Cell Locomotion

X-linked recessive inheritance
Duchenne muscular dystrophy
62
X-Linked recessive - Duchenne Muscular Dystrophy

63
• Severe Combined Immunodeficiency (SCID) with
Thrombocytopenia and Eczema. X-linked recessive
• A disease of defective reorganization of the actin
cytoskeleton Genetic defect: Mutation in the WAS
protein expressed in white blood cells and
megakaryocytes.
• Symptoms: –Thrombocytopenia, small platelet
size (decreased production of platelets in bone
marrow, increased destruction in spleen).
WISKOTT-
ALDRICH
SYNDROME
(WAS)

7. Cilia & Flagella
• Provide motility
Crawling is accomplished via actin filaments and protein myosin.
i. Cilia
• Movement: Propel
• Used to move substances outside
• Short & arranged in rows on surface of cell
ii. Flagella
• Whip-like extensions; sperm cells
• Movement: undulate
64
8. Centrioles
• Pairs of rod-shaped microtubular structures
• Direct formation of mitotic spindle during cell division
Thin, hair-like biological structures called cilia are tiny but mighty. Working
together, cilia play essential roles in human health, such as sweeping debris from
the lungs. Credit: Zvonimir Dogic, Brandeis University

9. Nucleus (Central Government)
Structure
1. Nuclear envelope –
isolates cell’s genetic
material, DNA from cytoplasm
2. Nucleoplasm –
fluid of the nucleus
3. Nucleolus (plural nucleoli)
Area of condensed DNA
Holds chromatin + ribosomal
subunits (region of intensive
ribosomal RNA synthesis)
• Subunits exit the nucleus via
nuclear pores
• Form ribosomes

Function
• contain genetic material, DNA
• DNA directs/controls the
activities of the cell
• DNA determines which types of
RNA are made (Transcription)
• The RNA leaves the nucleus and
directs the synthesis of
proteins in the cytoplasm
9. Nucleus (Central Government)

Nucleus: DNA, Chromatin, Chromosome
67
• Different levels of DNA condensation.
(1) Double stranded DNA.
(2) Chromatin strand (DNA with histones).
(3) Chromatin during interphase with centromere.
(4) Condensed chromatin during prophase. (2 copies of DNA molecule now)
(5) Chromosome during metaphase(only during cell division).
http://www.academickids.com/encyclopedia/index.php/Chromosome

10.
Endomembrane
System (ES)
(Production Factory)
68

(Production Factory)
Structure
• a series of membrane sacs
throughout cytoplasm
• divides cell into compartments
where different cellular functions
occur
1. Endoplasmic Reticulum (ER)
Rough & Smooth
2. Golgi Apparatus
3. Transport vesicles
e.g. Lysosomes, Peroxisomes,
Secretory Vesicles, Vacuoles
69

Function
1) Modifying protein chains
2) Synthesizing of lipids
3) Packaging of fully modified proteins & lipids into
vesicles for export or use in the cell
 And MUCH more to DISCOVER!
70

• Continuous network of flattened membrane
sacs create a “maze” throughout the cytoplasm
• ER responsible for protein synthesis, protein
folding, and protein transport (within cells).
Also responsible for the production and
storage of steroids, glycogen, and other
molecules.
• Helps move substances within cells
• 2 types
i. Rough endoplasmic reticulum (RER)
ii. Smooth endoplasmic reticulum (SER)
71

•RER Structure
Attachment of ribosomes gives a rough appearance
Ribosomes attached to surface
• Manufacture proteins
• RER Function
Proteins are modified as they move through the RER
Once modified, proteins in a form of glycoprotein are
packaged in vesicles and transported to the Golgi body
72

• SER Structure
Tubular membrane structure which continuous from RER
No ribosomes attached
• SER Function
Rich in enzymes that help to build molecules and
plays a role in metabolic processes e.g.
i. carbohydrates synthesis
ii. lipids : oils, phospholipids, steroids; cholesterol synthesis & breakdown
iii. detoxify drugs and poison in liver
iv. stores calcium ions esp in muscles cells.
• When a nerve impulse stimulates a muscle cell, calcium ions rush from the
ER into the cytosol, triggering contraction.
• Muscle cells have a specialized smooth ER that pumps calcium ions from
the cytosol and stores them in its cisternal
73
10. Smooth ER (SER)

• Nascent proteins (newly
synthesized & before folds into
its active shape) folded with
the assistance of ER
chaperones, and only
correctly folded proteins are
transported OUT to the Golgi.
• Unfolded or misfolded
proteins are retained in the ER,
retrotranslocated to the cytosol
for proteasomal degradation by
Endoplasmic-reticulum-
associated protein degradation
(ERAD) causing ER STRESS
74
10. ER Function

10. ER Stress
• ER stress: When cells synthesize
secretory proteins in amounts that
exceed the capacity of the folding
apparatus and Endoplasmic-
reticulum-associated protein
degradation (ERAD) machinery,
unfolded proteins are accumulated
in the ER.
• Unfolded proteins exposed
hydrophobic amino-acid residues
and tend to form protein
aggregates.
• Finally, this evokes ER stress and
prolonged ER stress trigger to cell
APOPTOSIS
75

10. ER Stress-Related Disease
1. Neurodegenerative
disease
AD, PD, polyQ disease,
Prion disease, ALS
2. Bipolar disorder
3. Diabetes mellitus
4. Atherosclerosis
5. Inflammation
6. Ischemia
7. Heart disease
8. Liver disease
9. Kidney disease
10. Viral infection
11. Many more….
77

10. Role of ER Stress in Endothelial
Dysfunction (ED)
79
Different noxious agents,
e.g., hyperlipidemia,
hyperhomocysteinemia,
hyperglycemia and
chronic inflammation,
induce ED promoting an
amplified ER stress
response as established
by several studies.
ER stress response
plays a central role in the
pathogenesis of ED and
consequently, CVD.

Types of Proteins
ENZYMES – catalyzes covalent bond breakage or formation
REGULATORY – bind to DNA to switch genes on or off
STRUCTURAL – collagen, elastin, keratin, etc.
MOTILITY – actin, myosin, tubulin, etc.
TRANSPORT – carries small molecules or irons
STORAGE – ovalbumin, casein, etc.
HORMONAL – insulin, nerve growth factor (NGF), etc.
RECEPTORS – hormone and neurotransmitter receptors
SPECIAL PURPOSE PROTEINS – green fluorescent protein, etc.
83

• Stack of flattened
interconnected membrane
sacs whereby proteins from ER
further processed and sorted
for transport to next stations:
lysosomes, the plasma
membrane, or secretion.
• Sorts, Tags and Packages fully
processed proteins and lipids
in vesicles and ship it to
different parts of the cell
84
10. ES: Golgi Apparatus (Post Office)

1. Proteins & lipids may be
Modified as pass through
layers of Golgi; glycolipid
2. Produces different
packages
i. Secretory vesicles
ii. Cell membrane
components
iii. Lysosomes
85
10. ES: Golgi Apparatus (Post Office)

• Vesicles form naturally e.g. secretion (exocytosis),
uptake (phagocytosis & endocytosis) and can fuse
with other organelle
• Perform many functions, e.g. organizing cellular
substances, metabolism, transport, buoyancy
control, and enzyme storage.
• EQUILIBRIUM inside and outside as malfunction can
cause potential hazardous / fatal conditions.
• DYSFUNCTION is thought to contribute to
Alzhemer’s disease, diabetes, certain epilepsy, some
cancers and immunological disorders, and certain
neurovascular conditions.
• ARTIFICIAL Vesicles are called LIPOSOMES
87
10. ES: Vesicles (Logistic)
The vesicles enclose a
cargo (green dots) that
e.g. neurotransmitters,
dye, drugs,
nanoparticles

10. ES: Lysosome (DBKL)
Structure - digestive system cell membrane bound contain
digestive enzymes to break macromolecules
• Lysosomes fuse with food vacuoles to become nutrients of cell
• Lysosome work best at pH 5
However digestive enzymes won’t
function well if some leak into cytosol
(pH difference)= Don’t Want To
Digest Yourself!
88

89
• Function
• little “Stomach” of the cell
• digests macromolecules
• “Sewerage System” of the cell – Digestion
• cleans up broken down organelles / old cells parts
• Transporter
• Transports undigested material to cell membrane for
removal (Exocytosis)
• Army Force
• Digests invaders or foreign matter that the cell has
engulfed by phagocytosis
• Physician
• Aid in cell renewal
Where
old organelles
go to die!
10. ES: Lysosome (DBKL)

But at times cells need to die...
• Lysosomes used to kill cells when they are
supposed to be destroyed
• Apoptosis - programmed destruction of cells
“auto-destruct” where lysosomes break open & kill cell
• ex: if cell grows uncontrollably this self-destruct mechanism is
triggered to remove damaged cell
• cancer must over-ride this to enable tumor growth
• some cells have to die for proper
development in an organism
• E.g: tadpole tail gets re-absorbed when it turns into a frog
• E.g: loss of webbing between your fingers during fetal
development
90

When things go bad…
93
• Lysosomes Diseases are often fatal
• digestive enzyme not working in lysosome
• genetic failure to manufacture an enzyme needed
• picks up biomolecules, but can’t digest one
• lysosomes fill up with undigested material (accumulation of
macromolecules (proteins, lipids, polysaccharides)
• grow larger & larger until disrupts cell & organ function
• Neurons of the central nervous system are
particularly susceptible to damage.

Lysosomal Storage Diseases
•LSD > 40 known diseases
•ex: Tay-Sachs disease
build up undigested fat in brain cells
• In Tay-Sachs disease a lysosomal enzyme
that breaks down gangliosides, a lipoprotein
found in neural tissue, is missing, and
gangliosides accumulate in the cells of the
brain resulting in mental retardation and
blindness.
• About 1 in 30 American Jews carry gene for
Tay-Sachs in chromosome 15. 94
Gangliosides are enriched in cell membrane
play important roles in the modulation of
membrane proteins and ion channels, in
cell signaling and in the communication
among cells

Common LSD include
• Fabry disease – known as X-linked genetic disease but affect
both genders with kidney, heart and pulmonary problems,
chronic pain and typical skin sign
• Gaucher disease – progressive LSD causing enlargement of
spleen, liver and bone lesions also affect the brain causing
severe neurological problems
• Mucopolysaccharidosis (I-VII) –accumulation of
mucopolysaccharides in causing progressive multiple organs
& systems damage- heart, bones, joints, central nervous
system & respiratory system. Signs & symptoms may not be
seen at birth, develop with age as more cells become
damaged by the accumulation of cell materials
95

Common LSD include
• Niemann-Pick C disease – results in progressive neurological
condition along with enlargement of the spleen and liver, as well
as lung disease
• Pompe disease - an often fatal is presented in infancy with
storage disease in which glycogen builds up mainly in the heart,
initially also known as acid maltase deficiency. If it manifests in
childhood and adulthood, Pompe can cause progressive
shoulder, hips and respiratory muscles
• Metachromatic leukodystrophy and Krabbe disease –
devastating LSD that result in progressive and neurodegerative
diseases. When presented in adulthood are associated with
neuropathies and psychiatric problems.
96

http://vcell.ndsu.nodak.edu/animations/p
roteintrafficking/movie-flash.htm
We hope that you enjoyed
your trip through the
Endomembrane System!
Have a
nice
day!
100

11. Mitochondria (Powerhouse)
101
2 membranes
 outer membrane - smooth
 inner membrane - highly folded
with layers called cristae
 inner membrane - matrix is within
containing their own DNA
The Mitochondria- responsible for energy production (power supplier
that provides energy to your home).
If the mitochondria is defective, your body cannot function as it should.

Unique Aspects of Mitochondrial Genetics
• mtDNA is maternally inherited and do not recombine.
• uniparental inheritance of disease mutations,
• Heteroplasmy - mixture of mutant & normal mtDNAs
• mtDNA get mutations 6 - 7 times the rate of nuclear DNA
as:
i. It lack protective histones.
ii. It is in close proximity to the electron transport chain, exposing it to
high concentrations of free radicals, which can damage the
nucleotides.
• Primary mitochondrial disease: Tissues with high aerobic demands
– Neuron (brain, esp. basal ganglia, special senses and autonomic neuron)
– Muscle (skeletal, cardiac, or smooth) 102

Diagnosis: Symptoms
• 100s of different diseases
genetically
• Even in individuals with the
same mutation, there are
different symptoms
• Change over time
• Challenging to diagnose
• Challenging to treat
103
Potential link between environmental and genetic
factors, and Parkinson's disease

SYSTEM CLINICAL MANIFESTATIONS
Cardiovascular
 heart failure
 arrhythmias
 sudden death
 left ventricular myocardial
noncompaction
Pulmonary
 dyspnea
 orthopnea
 respiratory failure
 respiratory acidosis
Neurologic
 atypical cerebral palsy
 movement disorders
 seizure disorder
 mental retardation
 stroke like episodes
 migraine
 dementia
Endocrine
 diabetes mellitus
 diabetes insipidus
 hypothyroidism
 hypoparathyroidism
 ACTH deficiency
SYSTEM CLINICAL MANIFESTATIONS
Ocular
 optic atrophy
 external opthalmoplegia
 ptosis
 retinitis pigmentosa
 cataract
Musculoskeletal
 myopathy
• Skeletal muscle :
ocular>axial/proximal>bulbar>distal
• Smooth muscle : dysphagia
• Cardiac : cardiomyopathy
 myalgias
Renal
 renal tubular defects
 benign renal cysts
 focal segmental glomerulosclerosis
 nephritic syndrome
Hemato-
logical
 anemia
 leukopenia
 thrombocytopenia
 eosinophilia
Gastro-
intestinal
 malabsorption
 villous atrophy
 pseudo-obstruction
Problems
That
May
Be
Associated
with
Mitochondrial
Cytopathies
105

There is NO CURE for mitochondrial disease
• Some helpful treatments include vitamins such as thiamine (B1), riboflavin (B12),
vitamin C, and vitamin E. Lipoic acid and coenzyme Q-10 are useful supplements.
• Some researchers are examining using drugs to block lactic acid buildup in the body
that is common in mitochondrial disease.
• Others try very low carbohydrate diets to reduce the workload for mitochondria.
108

Stages of
Disease
at the
Cellular
Level
109

Teaching
Message 4:
Cells divide &
make more
cells to help us
grow & repair
in a process
called mitosis.
111
111
Mitosis: Cell Dividing Process
Each cell divides into 2 identical cells.
Many cells in the human body
continuously die (e.g. in our bones,
blood, skin). Mitosis allows those cells
to be replaced

Teaching
Message 5:
Cells differentiate to
become specialized
cells to perform
specialized functions
which result in
different types of
cells e.g muscle cells,
nerve cells blood
cells, & etc.
112
112
The Nerve Cell
Red Blood Cells

Muscle Cells
113
Egg and Sperm Cells

Teaching
Message 6:
Different cell types
group together to
form organs and
organ systems. All
systems work
together to form a
living and
functional
organism.
114
114

Passive vs Active
Transport
115

Passive Transport
Particles tend to distribute evenly within a solution
Movement is from high to low concentration
No external /chemical source of energy is required
3 Types of diffusion
1. Osmosis – simple diffusion of water
• Highly polar water easily crosses the plasma membrane
2. Filtration
• Water and solutes are forced through a membrane by fluid, or
hydrostatic pressure
• A pressure gradient must exist
3. Facilitated diffusion
• Substances require a protein carrier for passive transport
117

Active Transport
Move against a concentration gradient
2 Types
1. Solute pumping
 Amino acids, some sugars and ions are transported by solute pumps
 ATP energizes protein carriers, and in most cases, moves substances against
concentration gradients
2. Bulk transport
i. Exocytosisis - cell transports molecules out of the cell by expelling them
• Neuron transmitting
ii. Endocytosis - Extracellular substances are engulfed by being enclosed in a
membranous vesicle
• Phagocytosis – cell eating
• Pinocytosis – cell drinking
118

Adaptation of Cells to
Changing Conditions
Cellular adaptations refer to the changes
made by cells in response to various
stimuli or changes in their local
environment.
This can involve changing the number of
cells or their morphological appearance.
It can be physiological, where it occurs in
normal tissues or organs or pathological
i.e. occurring in disease states.
120

Changing Conditions
Control of cell populations
The size of cell populations depends on the rate of 3 factors:
1. Cell proliferation
2. Cell differentiation
3. Cell death by apoptosis
Ultimately, cell signaling results in one of 4 outcomes:
1. Cell survival, i.e. resistance of apoptosis
2. Cell division – cell enters the cell cycle
3. Cell differentiation – cell takes on specialized form and
function
4. Cell death via apoptosis
121

Changing Conditions
ADAPTIVE DISORDERS OF GROWTH:
SIZE & NUMBER:
 Atrophy
 Hypertrophy
 Hyperplasia
DIFFERENTIATION OF CELLS:
 Metaplasia
 Dysplasia
122

Atrophy:
Reduction in cell SIZE in response to
i. Diminished function
ii. Inadequate hormonal stimulation
iii. Reduced blood supply
E.g.
• Reduction of skeletal muscle size when
extremity is immobilized in a cast for a
prolonged period
• Shrinkage of breasts and genitals following
menopause due to diminished estrogen
secretion
123
Changing Conditions

Hypertrophy:
Increase in cell SIZE without increase in cell
number
• Muscles of a weightlifter
• Right ventricular hypertrophy in response
to pulmonary hypertension
• Compensatory hypertrophy in paired
organs such as the kidneys, where one
organ is removed or dysfunctional and
the other hypertrophies to increase its
functional ability
• Expansion of the pregnant uterus
(combination of hypertrophy and
hyperplasia) 124
Changing Conditions

Hyperplasia:
increase in both cell SIZE & NUMBER in
response to increased demand
• Epidermal thickening in eczema
• Endometrial proliferation under the
influence of oestrogen during the
menstrual cycle
• Goiter due to iodine deficiency.
Enlargement of thyroid gland try and
capture all the iodine it can, as to make
the right amount of thyroid hormone.
• Glandular tissue of breasts during
pregnancy in preparation for lactation to
increase hormones
125
Gingival Hyperplasia
Changing Conditions

Metaplasia:
Reversible CHANGE of one DIFFERENTIATED
cell type to another.
This occurs via altered stem cell
differentiation and thus metaplasia can only
occur in labile or stable tissues
(e.g. Surface epithelia - gut mucosa, Bone marrow -haematopoietic
cells and Hepatocytes, Osteoblasts)
E.g:
Bronchial pseudostratified ciliated
epithelium becoming stratified squamous
epithelium in response to cigarette smoke.
Stratified squamous epithelium in the
esophagus becoming gastric epithelium
when exposed to persistent acid reflux
(Barrett’s esophagus) 126
Changing Conditions

Dysplasia:
cell development and maturation
are DISTURBED & ABNORMAL
(Individual cells vary in size & shape)
E.g: chronic inflammation of epithelial
cells of uterine cervix may progress to
cervical epithelial dysplasia & neoplasia
Increased enzyme synthesis
E.g: Adaptive response as in
inactivating/detoxifying drugs or chemicals
through SER enzymes 127
Changing Conditions

Knowledge of Cell
Structure Plays a
Fundamental Role in
Guiding and Advancing
Research in the Fields
of Regenerative
Medicine and Tissue
Engineering.
128

129
Cell Selection and Sourcing
Cell Culture and Expansion
Cell Differentiation
Biomaterial Design
Bioreactors and Tissue Culture Systems
Tissue Vascularization
Functional Integration
Quality Control
Patient-Specific Approaches

1.Cell Selection and Sourcing: Understanding the structure of
different cell types is critical for selecting the most appropriate cells
for tissue regeneration. Researchers need to choose cells that are not
only capable of differentiating into the desired tissue but also have the
correct structural characteristics. For example, when aiming to
regenerate bone tissue, mesenchymal stem cells are chosen due to
their osteogenic potential and structural compatibility.
2.Cell Culture and Expansion: Knowledge of cell structure is
essential for culturing and expanding cells in vitro. Researchers must
create an environment that mimics the natural conditions found in the
body to encourage cell growth and maintain their structural integrity.
Proper culture techniques ensure that cells maintain their functionality
during expansion.
3.Cell Differentiation: Regenerative medicine relies on the
differentiation of stem cells into specific cell types. Understanding the
structural changes that occur during differentiation is crucial for
directing this process effectively. For instance, in the regeneration of
cardiac tissue, researchers need to know how cardiac stem cells
develop into mature cardiomyocytes with the appropriate structural
130

4. Biomaterial Design: Biomaterials used in tissue engineering must
be designed to mimic the structural properties of the native tissue.
Knowledge of cell structure informs the choice of materials, their
physical properties (e.g., stiffness, porosity), and the incorporation of
signaling molecules or growth factors to guide cells in forming tissue
with the correct architecture.
5. Bioreactors and Tissue Culture Systems: Bioreactors and
culture systems used in tissue engineering are designed based on an
understanding of cell structure and function. These systems provide
mechanical and biochemical cues to cells, encouraging tissue
development while maintaining the structural integrity of the growing
tissue.
6. Tissue Vascularization: Creation of functional blood vessels in
engineered tissues is critical for their survival and integration into the
host. Knowledge of cell structure and tissue organization informs
strategies for promoting angiogenesis (formation of new blood
vessels) within engineered tissues.
7. Functional Integration: To attain functional tissue regeneration,
131

8. Quality Control: In regenerative medicine, ensuring the structural
and functional quality of the regenerated tissue is essential.
Researchers use techniques such as histological analysis and
imaging (e.g., electron microscopy) to assess the structural
characteristics of the engineered tissue and confirm that it closely
resembles native tissue.
9. Patient-Specific Approaches: Knowledge of cell structure is used
to tailor regenerative therapies to individual patients. By analyzing a
patient's own cells and understanding their structure, researchers can
develop personalized treatment strategies that consider the patient's
unique cellular characteristics.
In conclusion, knowledge of cell structure is foundational to the
success of regenerative medicine and tissue engineering. It informs
the selection of appropriate cells, the design of biomaterials and
culture systems, the control of tissue differentiation, and the
evaluation of engineered tissues. This understanding enables
researchers to develop therapies that aim not only to replace
damaged or lost tissues but also to restore their structural and
functional integrity. 132

Now do you
think your
cells are
important?
133

Cell Structure & Function of Cellular Organelles

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