REVIEWER

CELL AND MOLECULAR BIOLOGY

BASIC PROPERTY OF CELLS

1. Organization: Cells are highly organized structures, with
specialized compartments and organelles that carry out
specific functions. This organization allows for efficient and
coordinated cellular processes.
2. Metabolism: Cells are constantly engaged in metabolic
activities, which involve chemical reactions that provide energy
and materials for growth, repair, and other cellular functions.
includes processes like:
•Anabolism: Building complex molecules from simpler ones.
•Catabolism: Breaking down complex molecules into simpler ones to
release energy
3. Responsiveness: Cells respond to stimuli from their
environment, such as changes in temperature, light, or
chemical concentration. This responsiveness allows cells to
adapt to changing conditions and maintain homeostasis.
4. Growth: Cells increase in size and complexity through the
process of growth. This involves synthesizing new molecules
and organelles, ultimately leading to cell division.
5. Reproduction: Cells reproduce by creating new cells through
processes like mitosis (for somatic cells) or meiosis (for germ
cells). This ensures the continuity of life and the propagation of
genetic information.
6. Heredity: Cells contain genetic material (DNA) that carries the
instructions for building and maintaining the organism. This
genetic information is passed from parent cells to daughter
cells, ensuring the transmission of traits across generations.
7. Homeostasis: Cells maintain a stable internal environment
despite external fluctuations. This involves regulating factors
like temperature, pH, and nutrient levels.
8. Adaptation: Cells can adapt to changing environments over
time through evolutionary processes. This allows organisms to
survive and thrive in diverse habitats.

CELLS POSSESES A GENETIC PROGRAM AND THE MEANS TO USE IT

Genetic Program: Organisms are built based on information encoded
in genes, which are made of DNA. The human genetic program is
vast, containing enough information to fill millions of pages of text.
Chromosomes: This massive amount of information is packaged into
chromosomes, which reside within the cell nucleus.
Genes as Recipes: Genes are more than just storage lockers for
information; they act as recipes for building cellular structures,
directing cellular activities, and even creating more copies of
themselves.
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Mutations: Changes in the genetic information, known as mutations,
can lead to variations among individuals. This variation forms the
foundation of biological evolution.
Scientific Achievement: Discovering how cells use and transmit their
genetic information is considered one of the greatest achievements
of science in the past century

CELLS ARE CAPABLE OF PRODUCING THEMSELVES

Mitosis – responsible for growth and repair in multicellular
organisms.
Meiosis – responsible for sexual reproduction.

WHY CELL DEVIDES?

• Growth
• Repair
• Reproduction
• Development
• Renewal

CELLS ENGAGE IN MECHANICAL ACTIVITIES

• Cells are dynamic and constantly moving.
• Transporting Materials (Red blood cells in our bloodstream)
• Assembling and Disassembling Structures (Protein, Ribosomes,
and enzymes)

EXAMPLE OF CELLULAR MECHANICAL ACTIVITIES

1. Muscle contraction
2. Cytoskeleton movement
3. Cilia and flagella movement
4. Cell division
5. Phagocytosis

CELLS ARE ABLE TO RESPOND TO STIMULI

Stimulus – is any change in the environment that can be detected by
an organism and elicits a response.
Single-celled Organisms: These organisms, like protists, exhibit
direct responses to stimuli. They can move away from obstacles or
towards food sources. Their reactions are visible and immediate.
Multicellular Organisms: Cells within plants and animals respond to
stimuli in more subtle ways. They don’t move as visibly, but they
react through internal processes.
Hans Driesch – In 1891, Driesch performed an important experiment:
the separation of developing sea urchinblastomeres. He discovered
that if the sea urchin blastomeres were separated at the 2–cell
stage, two complete but smaller than normal sea urchins would
develop.

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TWO FUNDAMENTALLY DIFFERENT CLASSES OF CELLS
1. Prokaryotic cells
- Bacteria cells
2. Eukaryotic cells
- Plant cells
- Animal cells

CHARACTERISTICS THAT DISTINGUISH PROKARYOTIC AND

EUKARYOTIC CELLS
 Both types of cells are bounded by plasma membranes of
similar construction that serve as a selectively permeable
barrier between the living and nonliving worlds.
 Internally, eukaryotic cells are much more complex both
structurally and functionally than prokaryotic.
 Both contain a nuclear region that houses the cell's genetic
material, surrounded by cytoplasm.
 The genetic material of a prokaryotic cell is present in a
nucleoid: a poorly demarcated region of the cell that lacks a
boundary membrane to separate it from the surrounding
cytoplasm
 In contrast, eukaryotic cells possess a nucleus: a region
bounded by a complex membranous structure called the
nuclear envelope.
 Basis for the terms prokaryotic (pro-before, karyon-nucleus)
 Eukaryotic (eu -true, karyon –nucleus).
PROKARYOTES VS. EUKARYOTES CELL SIMILARITIES & DIFFERENCES
 Prokaryotic cells are cells without a nucleus.
 Eukaryotic cells are cells that contain a nucleus.
 Eukaryotic cells have other organelles besides the nucleus. The
only organelles in a prokaryotic cell are ribosomes

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TYPES OF PROKARYOTIC CELLS
1. Archaea or archaebacteria
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 2. Bacteria or eubacteria

DOMAIN ARCHAEA AND DOMAIN BACTERIA

- Best known Archana are species that live in extremely
inhospitable environments, they are often referred to as
extremophiles.
- The halophiles (prokaryotes that live in extremely salty
environments, such as the Dead Sea.
- Acidophiles (acid-loving prokaryotes that thrive at a pH as
low as 0, such as that found in the drainage of abandoned
mine shafts);
- And thermophiles (prokaryotes that live at: very high
temperatures).
- Methanogens, these Archaea live in anaerobic environments
(lacking oxygen) and produce methane as a metabolic
byproduct.
- All other prokaryotes are classified in the domain Bacteria.
- This domain includes the smallest known cells, the
mycoplasma (0.2 µm diameter), which are the only known
prokaryotes to lack a cell wall and to contain a genome with
fewer than 500 genes.
- Bacteria are present in every conceivable habitat on Earth,
from the permanent ice shelf of the Antarctic to the driest
African deserts, to the internal con- fines of plants and
animals.
- Bacteria have even been found living in rock layers situated
several kilometres beneath the Earth's surface
CYANOBACTERIA
- are plantlike because they have chlorophyll-containing cells.
- Most of them are single- celled, some form filaments, while
others form spores.
- Cyanobacteria grow in ditches, esteros, or in moist places
like gardens and sidewalls where light is present.
- referred to as the 'blue-green algae'.
PROKARYOTIC DIVERSITY
- refers to the vast array of single-celled organisms that lack a
nucleus and other membrane-bound organelles. These
organisms, classified into two domains – Bacteria and
Archaea, are incredibly diverse, inhabiting every conceivable
environment on Earth, from the depths of the ocean to
boiling hot springs.

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MODEL ORGANISMS
- are species that are extensively studied to understand
biological processes. They are chosen because they are easy
to maintain, reproduce quickly, have a sequenced genome,
and share many genetic and biological traits with humans.
SIX MODEL ORGANISMS
- one prokaryote and five eukaryotes – have captured much of
the attention:
- a bacterium, E. coli;
- a budding yeast, Saccharomyces cerevisiae,
- a flowering plant, Arabidopsis thaliana;
- a nematode, Caenor- habditis elegans;
- a fruit fly, Drosophila melanogaster,
- a mouse, Mus musculus.

UNDERSTANDING CELLULAR DIMENSIONS AND FUNCTIONS

Cells
- Cells are generally small to maximize their surface area-to-
volume ratio. This ratio is crucial because it affects the cell’s

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 ability to efficiently exchange materials with its
environment.
- Cells are incredibly tiny, with most ranging from 1 to 30
micrometers in diameter.
- Surface Area to volume Ratio
- The surface area to volume ratio of a cell plays a crucial role
in its ability to exchange substances with its environment.
As cells grow larger, their surface area increases at a slower
rate than their volume. This creates a challenge for larger
cells, as they struggle to take in nutrients and expel waste
efficiently.
Diffusion
- Diffusion, the random movement of molecules, is another
critical factor in cell size.
Overcoming Size Limitations
- Some organisms have evolved strategies to overcome the
challenges of being large
- Giant Single-Celled Organisms: Acetabularia and Caulerpa
are excellent examples of organisms that defy the typical
small cell size. Acetabularia can grow to over 10 cm long,
while Caulerpa can reach several meters in length.
- Despite these constraints, some organisms have evolved
strategies to overcome the challenges of being large.
Importance of Diffusion
Synthetic Biology
- The field of synthetic biology aims to create a minimal living
cell from scratch, using the same molecular components
found in real cells.
- Synthetic biologists study the molecular building blocks of
life.

ADULT STEM CELLS

- Stem cells are defined as undifferentiated cells that are
capable of self-renewal, that is, production of more cells like
themselves, and multipotent, capable of differentiating into
two or more mature cell types.
- Hematopoietic stem cells in the bone marrow are an example
of an adult stem cell.

CHARACTERISTICS:
> Enabling healing, growth, and replacement of lost cells
> Used for regenerative medicine and tissue repair
> Isolated from adult tissue, such as bone marrow

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Example:
Adult Brain
Which is not known for its ability to regenerate.

Adult Human Heart

Contains stem cells that are capable of differentiating into the cells
that form both the muscle tissue of the heart and the heart's blood
vessels.

TYPES OF ADULT STEM CELLS

1. Hematopoietic stem cells
2. Mesenchymal stem cells

EMBRYONIC STEM CELL

- Much of the excitement has been generated in the field over
the past decade or two has come from studies on embryonic
stem (ES) cells, a type of cell isolated from very young
mammalian embryos.
- These are the cells in the early embryo that give rise to all of
the various structures of the mammalian fetus. Unlike adult
stem cells, ES cells are pluripotent; that is, they are capable
of differentiating into every type of cell in the body.

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Introduction to the Plasma Membrane

The outer walls of a house or car serve as strong barriers, but

living cells are protected by a much thinner and more fragile
structure: the plasma membrane, which is only 5-10 nm wide. To
match the thickness of a book page, you’d need about 5,000 plasma
membranes stacked together. This thinness means the membrane
isn’t visible under a light microscope; it wasn’t until the late 1950s,
with advancements in staining and electron microscopy, that it
could be seen. Early electron micrographs revealed the plasma
membrane as a three-layered structure, with darkly staining inner
and outer layers.

The plasma membrane, as well as nuclear and cytoplasmic

membranes, exhibit a consistent ultrastructure with two dark-
staining layers and a lightly staining middle layer. Early electron
micrographs sparked debate about the molecular composition of
these layers, central to understanding membrane structure and
function. The membranes contain a lipid bilayer, with the dark
layers corresponding to the inner and outer polar surfaces. Before
delving deeper into membrane structure, it’s essential to explore
the major functions of membranes in cellular life.

TRILAMINAR APPEARANCE OF MEMBRANE

A. Electron Micrographs
showing the three layered
structure of plasma
membrane of an
erythrocyte after staining
the tissue with uranium
and lead

B. The outer edge of a

differentiated muscle cell
grown culture showing the
similar trilaminar
structure of both the
plasma membrane (PM)
and the membrane of the Sarcoplasmic reticulum (SR) a
calcium-storing compartment of the cytoplasm.

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MEMBRANE FUNCTIONS

1. Compartmentalization: Cell membranes enclose distinct

compartments, allowing specialized activities to occur
independently and enabling regulation without external
interference.

2. Scaffold for biochemical activities: Membranes act as

scaffolds for biochemical activities, organizing embedded
components for effective interactions, unlike reactants in
solution that rely on random collisions.

3. Selectively permeable barrier: Membranes act as selectively

permeable barriers, preventing unrestricted molecule
exchange while facilitating communication between
compartments. They function like a moat with gated
bridges, allowing selective movement in and out of the cell.

4. Solute Transport: The plasma membrane contains

mechanisms for transporting substances from low to high
concentration, allowing cells to accumulate essential
nutrients like sugars and amino acids. It also transports

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 specific ions, crucial for establishing ionic gradients,
particularly in nerve and muscle cells.

5. Response to external stimuli: The plasma membrane is

essential for signal transduction, containing receptors that
respond to external stimuli. These interactions trigger
internal responses, such as producing glycogen or
regulating calcium release.

6. Cell-cell communication: The plasma membrane mediates

cell-cell communication in multicellular organisms, allowing
cells to recognize, signal, and adhere to one another. It also
facilitates the exchange of materials and information and
connects extracellular materials to the intracellular
cytoskeleton.

7. Energy Transduction: Membranes are crucial for energy

transduction, converting one type of energy to another. In
photosynthesis, sunlight is absorbed by membrane-bound
pigments and converted into chemical energy stored in
carbohydrates. They also facilitate the transfer of chemical
energy from carbohydrates and fats to ATP, with this
machinery located in chloroplasts and mitochondria in
eukaryotes.

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MEMBRANE FUNCTION IN PLANT CELL

1.Compartmentalization

2. Scaffold for biochemical activities

3. Selectively permeable to water

4. Solute Transport

5. Response to external stimuli

6. Cell-cell Communication

7. Energy Transduction

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Brief History of Studies on Plasma Membrane Structure

•The first insights into the chemical nature of the outer boundary
layer of a cell were obtained by Ernst Overton of the University of
Zürich during the 1890s. He proposed that cell membranes were
made of lipids.

•He discovered that the more lipid soluble the solute, the more
rapidly it would enter the root hair cells.

• In 1900, Langmuir found out that there is one additional molecule

attached to it.

•The first proposal that cellular membranes might contain a lipid

bilayer was made in 1925 by two Dutch scientists, E. Gorter and F.
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Grendel. These researchers extracted the lipid from human red
blood cells and measured the amount of surface area the lipid.

The Chemichal Composition of Membranes

• Membranes are lipid-protein assemblies in which the components

are held together in a thin sheet by noncovalent bonds.
• The core of the membrane consists of a sheet of lipids arranged in
a bimolecular layer.

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 • The lipid bilayer serves primarily as a structural backbone of the
membrane and provides the barrier that prevents random
movements of water-soluble materials into and out of the cell. • The
proteins of the membrane, on the other hand, carry out most of the
specific functions.
• The ratio of lipids to proteins in a membrane varies, depending on
the type of cellular membrane (plasma vs. endo-plasmic reticulum
vs. Golgi), the type of organism (bacterium vs. plant vs. animal), and
the type of cell (cartilage vs. muscle vs. liver).

Membrane lipid

• Membranes contain a wide diversity of lipids, all of which are

amphipathic; that is, they contain both hydrophilic and hydrophobic
regions.

3 Main types of Membrane Lipids

1. Phosphoglycerides

2. 2. Sphingolipids

3. 3. Cholesterol

Phosphoglycerides

• Most membrane lipids contain a phosphate group, which makes

them phospholipids. Because most membrane phospholipids are
built on a glycerol back-bone, they are called phosphoglycerides.

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Unlike triglycerides, which have three fatty acids and are not
amphipathic, membrane glycerides are diglycerides-only two of the
hydroxyl groups of the glycerol are esterified to fatty acids; the
third is esterified to a hydrophilic phosphate group.

Membrane phosphoglycerides have an additional group linked to the

phosphate,

• Choline ~> phosphatidylcholine, PC

• Ethanolamine ~> phosphatidylethanolamine, PE

• Serine ~> phosphatidylserine

• Inositol ~> phosphatidylinositol, PI

Phosphoglycerides Structure

Spingolipids

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•A less abundant class of membrane lipids, called sphingolipids, are
derivatives of sphingosine, an amino alcohol that contains long
hydrocarbon chain.

• Sphingolipids consist of sphingosine linked to a fatty acid by its

amino group. This molecule is a ceramide. • If the substitution is
phosphorylcholine, the molecule is sphingomyelin, which is the only
phospholipid of the membrane that is not built with a glycerol
backbone.

• if the substitution is a carbohydrate, the molecule is a glycolipid.

• if the carbohydrate is a simple sugar, the glycolipid is called a

cerebroside

• if it is a small cluster of sugars that includes sialic acid, the

glycolipid is called a ganglioside.

Chemical Structures of Membrane Lipids

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Cholesterol

•Another lipid component of certain membranes is the ‘sterol’

cholesterol. Which in certain animal cells may constitute up to 50
percent of the lipid molecules in the plasma membrane. Plant cells
contain cholesterol like sterols, but biologists disagree as to
whether they completely lack cholesterol. Cholesterol molecules are
oriented with their small hydrophilic hydroxyl group toward the
membrane surface and the remainder of the molecule embedded in
the lipid bilayer.

•The hydrophobic rings of a cholesterol molecule are flat and rigid,

and they interfere with the movements of the fatty acid tails of the
phospholipids.

Nature and Importance of lipid bilayer

•Lipids are a variety of organic molecules grouped together on the

basis of their solubility in nonpolar solvents. Their varied biological
functions include energy source, energy storage, cell membrane
structural components, hormones, vitamins, vitamin absorption,
protection, and insulation.

•The lipid bilayer (or phospholipid bilayer) is a thin polar membrane

made of two layers of lipid molecules. These membranes are flat
sheets that form a continuous barrier around all cells.

•Biological bilayers are usually composed of amphiphilic

phospholipids that have a hydrophilic phosphate head and a
hydrophobic tail consisting of two fatty acid chains.

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The three main structures phospholipids form in solution; the
liposome (a closed bilayer), the micelle and the bilayer.

Function:

•The lipid bilayer is the barrier that keeps ions, proteins and other
molecules where they are needed and prevents them from diffusing
into areas where they should not be.

•Lipid bilayers are ideally suited to this role, even though they are
only a few nanometers in width, because they are impermeable to
most water-soluble (hydrophilic) molecules

The four main groups of lipids include:

1. Fatty acids (saturated and unsaturated)
2. Glycerides (glycerol-containing lipids)

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3. Nonglyceride lipids (sphingolipids, steroids, waxes)
4. Complex lipids (lipoproteins, glycolipids)

•Fatty acids and lipid derivatives play a role in cell signaling

pathways, regulating inflammation and immune responses. Fatty
acids do not dissolve in water; instead they are dispersed by the
formation of micelles in water.

Glycerides are lipid esters of the glycerol molecule and fatty acids.
The primary function of the glycerides is energy storage.
Triglycerides, store energy in fat cells, providing a long-term energy
source.

•Steroids are lipids with the principle function of signaling chemical

biological activities. Cholesterol is the most abundant steroid, and it
is the precursor for all the other important steroids of mammalian
metabolism. It is amphipathic.

•Complex lipids are bonded to other types of molecules. Because

lipids are mostly insoluble in water, the movement of lipids from
organ to organ through the bloodstream is facilitated by plasma
lipoproteins.

Energy Storage: Lipids, particularly triglycerides, store energy in fat

cells, providing a long-term energy source.

Cell Membrane Structure: Phospholipids are a key component of cell

membranes, creating a barrier and helping regulate what enters and
exits the cell.

Insulation and Protection: Lipids provide insulation to maintain body

temperature and cushion organs..

Hormone Production: Certain lipids, like cholesterol, are precursors

for steroid hormones such as estrogen, testosterone, and cortisol.

THE ASYMMETRY OF MEMBRANE LIPIDS

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•Lipid asymmetry provides the two sides of the plasma membrane
with different biophysical properties and influences numerous
cellular functions.

•The lipid bilayer consists of two distinct leaflets that have dis
tinctly different lipid compositions. One line of experiments that
have led to this conclusion take advantage of the fact that lipid-
digesting enzymes cannot penetrate the plasma mem brane and,
consequently, are only able to digest lipids that reside in the outer
leaflet of the bilayer.

Membrane Proteins

Depending on the cell type and the particular organelle within that
cell, a membrane may contain hundreds of different pro- teins. Each
membrane protein has a defined orientation relative to the
cytoplasm (as in Figure 4.40), so that the properties of one surface
of a membrane are very different from those of the other surface.

Integral proteins- that penetrate the lipid bilayer. They are

transmembrane proteins; that is, they pass entirely through the
lipid bilayer and thus have domains that protrude from both the
extracellular and cytoplasmic sides of the membrane.
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Peripheral proteins- that are located entirely outside of the lipid
bilayer, on either the cytoplasmic or the extracellular side, yet are
associated with the surface of the membrane by noncovalent bonds.

Lipid-anchored proteins- that are located outside the lipid bilayer,

on either the extracellular or the cytoplasmic surface, but are
covalently linked to a lipid. molecule that is situated within the
bilayer.

MEMBRANE LIPIDS - are amphipathic molecules, Most of which

spontaneously form bilayer.

Two types of lipids

1. PHOSPHOLIPIDS

A phospholipid is composed of a glycerol backbone attached on one

end to two fatty acids and the other end has the esterified
phosphoric acid and an organic alcoholic group.

2. CHOLESTEROL

• Controls fluidity of the membrane

• At modest concentration - decreases fluidity of the membrane
• At high concentration - increases fluidity of the membrane.

MEMBRANE FLUIDITY
• The property of the cell membrane that allows it to adapt its shape
and movement to different conditions.

MPORTANCE OF MEMBRANE FLUIDITY

• Compromises between a completely rigid structure with no
mobility and a completely fluid non viscous liquid without structural
organisation and strength.

• Allows interactions to take place in membrane.

•Because of fluidity moleculles that interact can come together.

carryout necessary reactions, and move apart.

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• Many of cell's basic functions, including cell movement, cell
growth, cell division, formation of intercellular junction. secretions,
and endocytosis, depend on the movement of membrane
components, which is achieved by fluidity.

MAINTAINING MEMBRANE FLUIDITY

- The internal temperature of most organisms (other than birds and

mammals) fluctuates with the temperature of the external
environment. Because it is essential for many activities that the
membranes of a cell remain in a fluid state, cells respond to
changing conditions by altering the types of phospholipids from
which they are made.

LIPID RAFTS - are microdomains within cell membranes composed

of cholesterol and sphingolipids, which form more ordered
structures than surrounding phosphoglycerides. These rafts can
concentrate specific proteins, like GPI-anchored proteins.

THE DYNAMIC NATURE OF THE PLASMA MEMBRANE

Lipid bilayer exists in a relatively fluid state,

allowing phospholipids to move within

the same leaflet.

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•Flip-flop of phospholipids between leaflets

is highly restricted but assisted by enzymes

called flippases, maintaining

membrane asymmetry.

•The mobility of membrane proteins is

crucial for membrane dynamics,

contributing to the fluid mosaic model.

CELL FUSION AND PROTEIN MOBILITY

•Cell fusion experiments show that

membrane proteins can diffuse

within the plane of the membrane.

•Larry Frye and Michael Edidin's

experiments (1970) demonstrated

protein mobility by fusing mouse

and human cells and tracking

membrane proteins over time.

Restrictions on Protein and Lipid Mobility

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Fluorescence Recovery After Photobleaching (FRAP) and Single-
Particle Tracking (SPT) are techniques designed to study the
movement of proteins or other molecules within biological
membranes, focusing on how they move and interact within their
environment.

FRAP measures collective movement of a population of proteins,

while SPT gives detailed insights into the movement of individual
proteins.

> The mobility of proteins and lipids within the cell membrane is not
unrestricted, as several factors impose constraints:

1.Membrane Composition

Lipid Rafts: Membranes are not uniform; certain areas, called lipid
rafts, are enriched in cholesterol, and specific proteins, which
restrict the mobility of lipids and proteins within these domains.

2. Cytoskeletal Interactions

Cytoskeletal Fencing: Proteins may interact with the underlying

cytoskeleton, which forms a "fence" that restricts their lateral
diffusion across the membrane.

3. Membrane Crowding

High concentrations of proteins in the membrane can lead to

crowding effects, limiting the diffusion and mobility of both proteins
and lipids.

4. Membrane Thickness and Curvature

Membrane Curvature Regions of the membrane with high curvature

can restrict protein and lipid movement due to physical constraints.

5.Temperature

Membrane fluidity is highly temperature-dependent. At lower

temperatures, lipids can transition to a gel-like phase, significantly
reducing the mobility of both lipids and proteins.

6. Protein-Protein Interactions

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Proteins often interact with each other to form complexes. When
proteins are bound together or oligomerized (grouped), they are
restricted in their movement because the larger structure is harder
to diffuse through the membrane.

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