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Cellular Level of Organization

BY: Dr. Tanvi H. Desai


(M.Pharm, Ph.D)
Introduction
• A cell is the basic, living, structural and functional unit of body enclosed by a
membrane.
• There are about 200 different types of cells in our body.
• All cells arise from existing cells by the process of cell division, in which one cell
divides into two identical cells.
• Cell biology is the study of cellular structure and function.
• For ease of study cells are divided into three main parts: Plasma membrane,
Cytoplasm, and Nucleus.
• 1. Plasma membrane: It forms outer flexible surface of the cell that separates its
internal environment from the external environment.
• This relative barrier regulates the flow of materials into and out of a cell.
• It plays a key role in communication among cells and between cells and their
external environment.
• 2. Cytoplasm : It consists of all cellular contents
between the plasma membrane and the nucleus.

• Cytoplasm has two components: cytosol and


organelles.

• (a) Cytosol : It is the fluid portion of cytoplasm,


contains water, dissolved solutes and suspended
particles.
• (b) Organelles: They are surrounded by cytosol.

• Each type of organelles has a characteristic shape and


specific functions.

• Examples include endoplasmic reticulum, Golgi


complex, lysosomes, peroxisomes, ribosomes,
mitochondria and cytoskeleton.
3. Nucleus: This large
organelle contains most of
cellular DNA.

• A single molecule of DNA is


associated with several
proteins to form a
chromosome (chromo=
colored), which contains
thousands of hereditary
units called genes.

• The genes control most


aspects of cellular structure
and function.
structures found in body cells
The Plasma Membrane
• The plasma membrane surrounds and contains the cytoplasm of a cell.

• It is a flexible yet strong barrier between the cell's environment and the extracellular environment.

• 1. Structure
• The membrane is composed of proteins and lipids (phospholipids) that are held together by non-
covalent forces.

• According to the fluid mosaic (mixture) model, the membrane is a mosaic of proteins floating like
icebergs in a lipid bilayer sea.

• The lipid bilayer consists of two back to back layers of phospholipids, cholesterol, and glycolipids.

• The bilayer arrangement occurs because of amphipathic (both polar and nonpolar parts) nature of
the lipids.

• Integral (important) proteins extend into or through the lipid bilayer.


• Peripheral proteins associate with membrane lipids are at the inner or outer surface of the
membrane.

• Many integral proteins are glycoproteins, with sugar groups attached to the ends that face
the extracellular fluid.
• Together with glycolipids, the glycoproteins form a glycocalyx on the extra cellular surface of
cells.
• 2. Functions
• Protection: It protects cells from injury.
• Barrier: It holds or bounds cell contents and maintains individuality of the cell.
• Shape of the cell: It anchors (support) structural elements of the cytoskeleton which
provide distinct shape to specific cells.
• Cell recognition: Glycoproteins and glycolipids function as receptors for specific chemical
signals (e.g., hormones) from outside and trigger specific processes within the cell, eg,
immune response, rejection of a substance and signal transduction.
• Cell junctions: Membrane proteins help adjacent cells to form various types of junctions for
keeping the cells together during formation of tissues.

• Microvilli: These are membrane evaginations specialized for increasing surface area for
absorption.

• Cell movements: Movements like undulations (fluctuation) (eg, fibroblasts) and


pseudopodia (over growth)(eg, macrophages) are performed by cell membrane. They also
form sheaths (covers ) around flagella and cilia.

• Enzymes: Some membrane proteins catalyze biochemical reactions.

• Transport proteins: Many membrane proteins form channels that facilitate the transport of
water (aquaporins), ions, and nutrients like sugars and amino acids.

• Selective permeability: It allows entry to only selected substances and is impermeable to


others.
• Bulk transport: The bulk intake of materials from outside by invagination of plasma
membrane to form vesicles is called endocytosis. Throwing out of waste products
and secretory materials by the reverse process is called exocytosis.

• Impulse transmission: Nerve impulses travel through the plasma membrane of


nerve cells.

•Cytoplasm
• It has two components: the cytosol and organelles.

• 1 Cytosol: It is the fluid portion of cytoplasm that contains water (75-90%), ions,
glucose, amino acids, proteins, lipids, ATP, and waste products.

• Some cells may contains storage products like lipid droplets and glycogen granules.

• It is the site of many chemical reactions required for a cell's existence, eg, enzymes
of glycolysis.
• Various cell organelles exchange materials among themselves only through it.
• It also exchanges materials with the extracellular environment.
• 2. Organelles: Organelles are specialized structures with characteristic shapes that
have specific functions.
• Organelles often cooperate to maintain homeostasis.
• Various types of cell organelles are as follows:
• 1. Ribosomes: Ribosomes (80s size) consist of two subunits in the nucleus and are
composed of ribosomal RNA (rRNA) and ribosomal proteins.
• Some ribosomes are attached to the outer surface of the nuclear membrane and to
the endoplasmic reticulum.
• Ribosomes are also located within mitochondria.
• Two subunits unite during protein synthesis.
• Functions:

• (a) Ribosomes associated with


endoplasmic reticulum (ER)
synthesize proteins destined
(appointed) for insertion (placing)
in the plasma membrane or
secretion from the cell.

• (b) Free ribosomes synthesize


proteins used in the cytosol.
• (c) Mitochondrial ribosomes
synthesize mitochondrial proteins.
• 2. Endoplasmic Reticulum (ER)
• ER is a network of membranes that form flattened interconnected sacs (cisternae) or
tubules.
• It extends from the nuclear envelope throughout the cytoplasm.
• The cell contains two distinct forms of the ER, which differ in structure and function.
• A. Rough ER: It is dotted with ribosomes that synthesize proteins. The proteins then
enter the space within the ER for processing and organization.
• Functions: Rough ER produces secretory proteins; forms glycoproteins; synthesizes
phospholipids; and attaches proteins to phospholipids.
• These are transferred into cellular organelles, inserted into the plasma membrane,
or secreted during exocytosis.
• B. Smooth ER lacks ribosomes and extends from RER to form a network of
membrane tubules. SER contains unique enzymes that make it functionally more
diverse than RER.
Functions: Smooth ER synthesizes
fatty acids and steroids, such as
oestrogens and testosterone;
inactivates or detoxifies drugs and
other potentially harmful substances;
removes the phosphate group from
glucose-6-phosphate; and stores and
releases Ca2+ ions that trigger
contraction in muscle cells.
• 3. Golgi complex:
• The Golgi complex consists of a stack of 3 to 20 cisternae that are small,
flattened membranous sacs with bulging ends.
• The cisternae are often curved, giving the Golgi complex a cuplike shape.
• The Golgi complex(es) is more extensive (wide) in cells that secrete proteins.
• Cisternae differ from each other in size, shape, and enzymatic activity.
• The convex entry or cis face of Golgi complex is a cisterna that faces the rough
ER.
• The concave exit or trans face is a cisterna that faces plasma membrane.
• The sacs between the entry and exit faces are called medial cisternae.
• Transport vesicles from ER merge to form
the entry face; cisternae are supposed to
mature, in turn become medial and then
exit cisternae.

• Functions:

• (a) Different enzymes in the entry, medial, and exit


regions of the Golgi complex permit each region to
modify, sort, and package proteins for transport to
different destination.

• (b) It forms secretory vesicles that discharge


processed proteins via exocytosis into extracellular
fluid.

• (c) It forms transport vesicles that carry molecules


to other organelles, such as lysosomes.
• 4. Lysosomes:

• Lysosomes are membrane enclosed vesicles that contain digestive enzymes.

• They are formed from the Golgi complex and contain as many as 60 kinds of
powerful digestive and hydrolytic enzymes. Lysosomal interior has a pH of 5 (100
times more acidic than that of the cytosol, i.e pH7).

• Endosomes, phagosomes, and pinocytic vesicles deliver materials to lysosomes for


degradation.

• Functions:

• (a) They digest substances that enter a cell via endocytosis and transport final
products of digestion into cytosol.
• (b) They carry out autophagy, the
digestion of worn-out organelles.

• (c) They can carry out autolysis,


the digestion of entire cells.
Thus, they are called "suicidal
bags".

• (d) They also carry out


extracellular digestion, eg, sperm
head releases lysosomal
enzymes that help its
penetration into the oocyte.
• 5. Peroxisomes:
• They are similar in structure to lysosomes but are smaller and contain several
oxidases, enzymes that can oxidize (remove hydrogen atoms from) various organic
substances, eg, amino acids and fatty acids.
• Functions:
• (a) As part of normal metabolism, they oxidize amino acids and fatty acids.

• (b) They oxidize toxic substances, such as alcohol in liver cells.

• (c) The hydrogen peroxide (H2O2) produced as a by product in the process of


oxidation is destroyed by the enzyme catalase.

• 6. Proteasomes:
• Proteasomes are tiny barrel shaped structures, many thousands in number, in both
the cytosol and the nucleus of a typical body cell.
• These recently discovered organelles contain proteases, enzymes that cut proteins into small
peptides.

• Functions:

• (a) They continually degrade unneeded, damaged, or faulty proteins into small peptides, which are
then broken down into amino acids by other enzymes.

• (b) Abnormal functioning of protesomes may result into accumulation of defective proteins, eg,
misfolded proteins accumulate in brain cells of people with Parkinson disease and Alzheimer
disease.

• 7. Mitochondria:

• A cell may contain hundred to several thousand mitochondria or "powerhouses" of the cell, which
generate most of cellular ATP through aerobic (O2 requiring) respiration.

• A mitochondrion consists of an outer mitochondrial membrane and an inner mitochondrial


membrane with a small fluid-filled space between them.
• Outer membrane is smooth, the inner
contains a series of folds called cristae, and
encloses a fluid-filed cavity called matrix.

• The matrix contains DNA (circular), RNAs,


ribosomes, and enzymes.

• Functions:

• (a) They generate ATP through reactions of


aerobic cellular respiration.

• (b) They can synthesize some of their


proteins, and can self replicate before cell
division.

• (c) They also take part in fat metabolism.


• 8. The Cytoskeleton:
• The cytoskeleton is a network of three types of protein filaments that extend through out
the cytosol : microfilaments, inter mediate filaments, and microtubules .
• Microfilaments are thin, composed of protein actin and are mostly widespread at the
periphery of the cell.
• Functions:
• (a) They help generate movement and provide mechanical support.
• (b) They are involved in muscle contraction, cell division, and cell locomotion.
• (c) They anchor the cytoskeleton to integral proteins in the plasma membrane.
• (d) They provide mechanical support to microvilli (nonmotile microscopic finger like
projections of the plasma membrane).
• Intermediate filaments are thicker than microfilaments.
• Several different proteins compose these exceptionally strong filaments.
• Functions: they help to stabilized the position of
organelles such as nucleus and help attach cells
to one another.

• Microtubules: These largest cytoskeletal


components are long, unbranched hollow tubes
composed mainly of the protein tubulin.
• Their assembly begins in the centrosome from
where they grow outward toward the periphery
of the cell.
• Functions:
• (a) They help to determine the cell shape.

• (b) They help in the movement of secretory


vesicles, of chromosomes during cell division,
and of specialized cell projections, such as cilia
and flagella.
• 9. Centrosome:

• The centrosome consist of a pair of


perpendicularly (up and down) placed
centrioles and pericentriolar material.

• Function:

• (a) The pericentriolar material


organizes microtubules in non dividing
cells and the mitotic spindle in the
dividing cells.

• (b) Centrosomes replicate during cell


division so that daughter cells have
the capacity for cell division.
• 10. Cilia and Flagella:
• These motile projections of the cell surface are formed by basal (bottom) bodies.
• Microtubules are the main components of cilia and flagella.
• The basal body is similar in structure to a centriole, lies just below the surface of
the plasma membrane and functions in initiating the gathering of a cilium or
flagellum.
• Cilia are numerous, short hairlike projections that extend from the surface of the
cell.
• A cilium displays an oar (paddle) like pattern of beating; it is relatively stiff during
the power stroke, but more flexible during the recovery stroke.
• Functions:
• (a) The coordinated movement of many cilia on the surface of a cell causes the
stable movement of fluid along the cell surface.
• They help to sweep foreign particles
trapped in mucus away from the lungs.

• (b) They help to sweep oocytes toward


the uterus.

• Flagella are similar in structure to cilia but


are typically much longer. Sperm cell's tail
is the only example of flagellum in the
human body.
• Functions:

• Flagellum moves the whole cell; it propels


the sperm toward the oocyte for
fertilization
Nucleus
• Structure:

• The nucleus consists of a double membrane nuclear envelope and is the


largest cell organelle.

• The nuclear envelope separates the nucleus from the cytoplasm.

• The outer nuclear membrane is connected to the rough ER.

• Many openings called nuclear pores extend through the nuclear envelope.

• Small molecules and ions move through the pores passively by diffusion.

• Most large molecules, such as RNAs and proteins, are selectively transported
by an active process through the nuclear pores into or out of the nucleus.
• One or more spherical bodies called nucleoli inside the nucleus function in
producing ribosomal subunits.

• They are sites of synthesis of rRNA.

• Nucleoli degenerate during cell division and reorganize once new cells are
formed.

• Nuclear matrix is a network of intermediate filaments that provides shape to


the nucleus and anchorage to the chromatin fibers.

• Chromatic reticulum (network of chromatin fibres) consists of DNA molecules


associated with nucleosomes. DNA wraps twice around each nucleosome.

• All the genes (hereditary units) arranged along chromosomes constitute the
genome of a cell or an organism.
• During cell division, the DNA replicates
(duplicates) and the duplicated chromatic fibres
of each chromosome condense by coiling,
forming a pair of chromatids linked together at a
point called centromere.

• Human somatic (body) cell has 46 chromosomes.

• Functions:

• (a) Nuclear pores control the movement of


substances between the nucleus and cytoplasm.

• (b) Nucleoli produce ribosomal subunits which


constitute ribosomes in the cytoplasm.

• (c) Chromosomes consist of genes that control


cellular structure and direct cellular functions.
Cell division
• Cell division is the process by which a parent cell divides into two or more daughter
cells.
• These cells divide once in approximately every 24 hours. The duration of cell cycle
can vary with organism and the two types of cell division are:
• Somatic cell division
• Reproductive cell division
• Somatic cell division: A cell undergoes a nuclear division called mitosis and a
cytoplasmic division called cytokinesis to produce two identical cells, each with the
same number and kind of chromosomes as the original cell.
• Reproductive cell division: A cell undergoes a division called as meiosis, in which the
number of chromosomes in the nucleus is reduced by half.
• This mechanism produces gametes the cells needed to form the next generation of
sexually reproducing organisms.
• Somatic Cell Division:
• Cell Cycle:
• The cell cycle is an orderly sequence of events by which a somatic cell duplicates its
contents and divides in two.
• Human cell, contain 23 pairs of chromosomes with a total of 46 chromosomes. One
member of each pair is inherited from each parent.
• The two chromosomes that make up each pair are called homologous
chromosomes. Somatic cells contain two sets of chromosomes; they are called
diploid cells, denoted as 2n.
• The cell cycle is divided into two basic phases:
• Interphase: When a cell is not dividing.
• Mitotic phase: When a cell is dividing

• Interphase: During interphase replication of DNA takes place and additional cell
organelles and cytosolic components are formed.
• Interphase is a state of high metabolic activity; it is during this time that the cell
grows.

• Interphase consists of three phases: G1, S, and G2.

• G1 phase: It is the interval between the mitotic phase and the S phase.

• During G1, the cell is metabolically active; it replicates most of its organelles and
cytosolic components but not its DNA.

• Replication of centrosomes also begins in the G1 phase.

• G1 phase lasts 8 to 10 hours.

• S phase: It is the interval between G1 and G2, lasts about 8 hours. During the S
phase, DNA replication occurs. As a result, the two identical cells formed during cell
division will have the same genetic material.
G₂ phase: It is the interval between the S
phase and the mitotic phase.

It lasts for 4 to 6 hours.

During G₂ phase, cell growth continues,


enzymes and other proteins are
synthesized in preparation for cell
division, and replication of centrosomes is
completed.

Once a cell completes its activities during


the G1, S, and G2 phases of interphase,
the mitotic phase begins.
• Mitotic (M) Phase:
• This is the most dramatic period of the cell cycle, involving a major reorganization of
virtually all components of the cell.
• Since, the number of chromosomes in the parent and progeny cells is the same, it is
also called as equational division.
• The mitotic phase of the cell cycle consists of a nuclear division (mitosis) and Human
Anatomy an cytoplasmic division (cytokinesis) to form two identical cells.
• The process results in the exact distribution of genetic information.

• It is divided into four stages:

• Prophase
• Metaphase
• Anaphase
• Telophase
• Prophase: In early prophase, the chromatin fibers condense and shorten into chromosomes.
• Each prophase chromosome consists of a pair of identical strands called chromatids.
• A constricted region called a centromere holds the chromatid pair together.
• At the outside of each centromere is a protein complex known as kinetochore.
• In late prophase, tubulins in the pericentriolar material of the centrosomes start to form the
mitotic spindle, a football shape of microtubules that attach to the Kinetochore.
• As the microtubules lengthen, they push the centrosomes to the ends of the cell so that the
spindle extends from pole to pole.
• The nucleolus disappears and the nuclear envelope breaks down.
• Metaphase: During metaphase, the microtubules of the mitotic spindle
align the centromeres of the chromatid pairs at the exact center of the
mitotic spindle called as metaphase plate.

• This arrangement of the chromosomes at the metaphase plate ensures that


each nucleus after cell division will receive one copy of each chromosome.
• Anaphase: During anaphase, the centromeres split, separating the two
members of each chromatid pair, which move toward opposite poles of the
cell.
• Once separated, the chromatids are termed chromosomes.
• As the chromosomes are pulled by the microtubules of the mitotic spindle
during anaphase appears V-shaped.
• Telophase: Telophase begins after chromosomal movement stops.
• The identical sets of chromosomes, now at opposite poles of the cell, uncoil
and forms thread-like chromatin.
• A nuclear envelope forms around each chromatin mass, nucleoli reappear and
the mitotic spindle breaks up.
• Cytokinesis: Division of a cell's cytoplasm and organelles into two identical cells is called
cytokinesis.
• Process usually begins in late anaphase with the formation of cleavage furrow, a slight
indentation of the plasma membrane, and is completed after telophase.
• <

• The cleavage furrow usually appears midway between the centrosomes and extends around
the periphery of the cell.
• Actin microfilaments that lie just inside the plasma membrane form a contractile ring that
pulls the plasma membrane progressively inward.
• When cytokinesis is complete, interphase begins.
• The sequence of events can be summarized as G1 phase →S phase→ G₂ phase → Mitosis→
Cytokinesis
Process of transport across the plasma membrane
• Passage of drug across cell membrane- The cell membrane acts as a biological barrier. The
following are the processes by which a drug can cross biological membrane.

• 1.Passive transport and 2. Specialized transport.

• 1.Passive transport- This transport is energy independent and no utilization of ATPs. The
four types of passive transports are diffusion, facilitated diffusion, filtration and osmosis.

• a. Diffusion (simple)- Diffusion is the net movement of drug molecules from an area of
high concentration to an area with lower concentration.

• The difference of concentration between the two areas is termed as the concentration
gradient, and diffusion will continue until this gradient has been eliminated.

• Diffusion across the cell membrane depends on concentration gradient and lipid solubility.
• Lipid solubility depends on ionization. Un-ionized drugs are more lipid soluble and are
better absorbed (more reabsorbed in the kidneys and less excreted). Ionized drugs are less
lipid soluble and are less absorbed (less reabsorbed in kidneys and more excreted).

• Ionization depends on pH of drug and pH of the medium (surrounding fluid). If the pH is


the same the drug remain unionized and become more lipid soluble and absorbed better.

• Acidic drugs like aspirin, barbiturates, etc. are better absorbed from the stomach. Alkaline
drugs like morphine, atropine, and chloroquine are better absorbed from the small
intestine.

• If pH is opposite-> drug is ionized-> less lipid soluble-> less absorption (e.g. alkaline drugs
are poorly absorbed in the stomach).
• b. Facilitated diffusion (carrier- mediated diffusion) - It is the movement
of drug molecules across the cell membrane via special transport
proteins that are present within the cellular membrane.

• Many large molecules, such as glucose, are insoluble in lipids and too
large to pass through the membrane pores. Therefore, it will bind with
its specific carrier proteins, and moved through the cellular membrane.
• c. pore transport: It is also called as bulk flow or filtration. The process is important
in the absorption of low molecular weight (less than 100), low molecular
size(smaller than diameter of the pore) and generally water soluble drugs through
narrow, aqueous filled channels or pores in the membrane structure. E.g urea,
water and sugars.

• Drug permeation through water- filled channels is of particular importance in renal


excretion, removal of drug from the cerebrospinal fluid and entry of drug into the
liver.
• d. Osmosis- Osmosis is the movement of water molecule through the cell
membrane (semi permeable membrane) from the region of higher water
concentration to the region of less water concentration is called osmosis.
• 2. Specialized transport- Specialized transport of drug across the cell
membrane requires carrier proteins.

• The drug forms a complex with the carrier proteins at the outer surface of
the cell membrane and then transported across the cell membrane to the
inner surface and the drug is released from the drug carrier complex.

• These are of two main types- active transport, and endocytosis.

• a. Active transport- In active transport, the drug molecule penetrates in the


lipid bilayer membrane from lower concentration to the higher concentration
of solutes against the concentration gradient by utilizing energy (ATP) and
with the help of carrier proteins.
• b. Transport in Vesicles:

• It is the movement of substance into or out of a cell in vesicles that sprout from
the plasma membrane. It requires energy of ATP (active transport).

• Endocytosis- Endocytosis is the movement of materials into a cell via


membranous vesicles. Endocytosis requires the expenditure of energy (ATP).
There are 3 types phagocytosis, pinocytosis and receptor mediated endocytosis.

• Phagocytosis- (cell eating) is movement of a solid particle into a cell after


pseudopods engulf it to form a phagosome, eg, itnake of bacteria, viruses, and
aged or dead cells.

• Pinocytosis (cell drinking) is movement of extracellular fluid into a cell by in


folding of plasma membrane to form a vesicle.
• Receptor mediated endocytosis- It is also called clathrin-dependent
endocytosis. The receptor present on the cell membrane binds with the
specific ligand. This ligand-receptor gets swallowed using clathrin molecules.
Ligands include transferrin, low-density lipoproteins (LDLs), some vitamins,
certain hormones, and antibodies.
• (b) Exocytosis : It is movement of substances out of a cell in secretory
vesicles that fuse with the plasma membrane and release their contents
into the extracellular fluid, eg, neurotransmitters, hormones and
digestive enzymes.

• (c) Transcytosis: It is movement of a substance through a cell as a result


of endocytosis on one side and exocytosis on the opposite side, e,g,
antibodies across endothelial cells.
CELL JUNCTIONS
• Cell junctions are also called as intercellular bridge.

• Cell junctions are contact points between the plasma membranes of tissue cells.

• Cell junctions consist of multi-protein complexes that provide contact between neighboring cells or between
a cell and the extracellular matrix.

• There are five different types of cell junctions:

• Tight junctions

• Adherens junctions

• Desmosomes

• Hemidesmosomes

• Gap junctions
• Tight Junctions: It acts as barriers that regulate the movement of water and
solutes between epithelial layers.
• The cells of epithelial tissues that line the stomach, intestines and urinary
bladder have many tight junctions to retard the passage of substances
between cells and prevent the leaking of contents into the blood or
surrounding tissues.
• Tight junctions present in different types of epithelia are selective for solutes
of differing size, charge and polarity.
• These are composed of a branching network of sealing strands acting
independently from the others.
• Each strand is formed from a row of trans-membrane proteins fixed in both
plasma membranes.
• The major proteins present are claudins and occludins.
• Functions: They hold the cells together.
• Tight junctions help to maintain the polarity of cells by preventing the lateral
diffusion of proteins between the apical and lateral/basal surfaces.
• Tight junctions prevent the passage of molecules and ions through the space
between plasma membranes of adjacent cells.
• Adherens Junctions: These are also called as intermediate junction or belt
desmosome.
• These are protein complexes that occur at cell-cell junctions in epithelial and
endothelial tissues.
• Adherens junctions contain plaque, a dense layer of proteins on the inside of the
plasma membrane that attaches both to membrane proteins and microfilaments of
the cytoskeleton.
• The trans-membrane glycoproteins present in adherens junctions called as
cadherins that joins the cells.
• In epithelial cells, adherens junctions forms the extensive zones called as adhesion
belts.
• Adherens junctions helps to epithelial surfaces to resist separation during various
contractile activities such as movement of food through the intestines.
• Desmosomes: Desmosomes contain plaque and trans-membrane glycoproteins
such as cadherins that extend into the intercellular space between adjacent cell
membranes and attach cells to one another.
• A desmosome plaque attaches to intermediate filaments.
• The intermediate filaments extend from desmosomes on one side of the cell across
the cytosol to desmosomes on the opposite side of the cell.
• Such a type of structural arrangement helps in the stability of cells and tissues.
• These types of junctions are more common in the epidermis (the outermost layer o
the skin) and cardiac muscle cells of the heart.
• Hemidesmosomes: Hemidesmosomes resemble like desmosomes but they
do not link the adjacent cells.
• The structure of hemidesmosomes is like half of a desmosome.
• The trans-membrane glycoproteins present in hemidesmosomes are integrins.
• To the inner side of plasma membrane, integrins attaches to the intermediate
filaments.
• To the outer side of plasma membrane, the integrins attaches to the protein
laminin present in the basement membrane.
• Hence, it plays an important role in fixing cells to the basement membrane.
• Gap Junctions: The membrane proteins present in gap junctions are called
as connexins, form tiny fluid-filled tunnels called connexons that connect
neighboring cells.
• The plasma membranes of gap junctions are separated by a very narrow
intercellular gap (2 to 4 nm).

• Through the connexons the ions and small molecules can diffuses from the
cytoplasm of one cell to another cell.

• A gap junction allows the communication of cells with one another.

• Gap junctions enable nerve or muscle impulses to spread rapidly among nervous
cells.

• Dissolved substances such as ions or glucose can pass through the gap junctions.
General principles of cell communication:
• All organisms, whether unicellular or multi cellular need to respond to their ever
changing environment in order to survive and flourish.
• Such responses are governed by the ability of cell to sense physical changes and
chemical cues occurring around them.
• The process of sensing and responding to extrinsic signals is often termed cellular
communication although scientist also use terms such as signal transduction or
signalling.
• Cells respond to a wide range of extrinsic signals that include chemical messengers,
electrical impulses, mechanical forces, pH, heat and light.
• Cell signalling:
• Cell signalling is part of complex system of communication that directs basic
activities of cells and coordinates cell actions.
• The ability of cells to observe and correctly respond to their microenvironment
is the basis of development, tissue repair, and immunity as well as normal
tissue homeostasis.

• Errors in cellular information processing are responsible for disease such as


cancer, autoimmunity and diabetes.

• Cell signalling involves:


• Detection of the stimulus on the surface of the plasma membrane

• Transfer of signal to the cytoplasmic side


• Transmission of the signal to effector molecules
• The final effect is to trigger a cells response, such as the activation of gene
transcription
Forms of Intracellular Signalling
• Cell signaling can be classified as mechanical and biochemical based on the type of the
signal.
• Mechanical signals are the forces applied on the cell and produced by the cell.
• Biochemical signals are produced by the biochemical molecules such as proteins, lipids, ions
and gases.
• These signals can be classified based on the distance between signaling and responder cells.

• Signaling between and amongst cells is divided into the following:


• Contact dependant signalling

• Paracrine signalling

• Synaptic signalling

• Autocrine signalling
• Contact Dependent Signalling:
• Gap junctions in animals are connections between the plasma membranes of
neighbouring cells.

• These water filled channels allow small signalling molecules, called intracellular
mediators, to diffuse between the two cells.

• Small molecules, such as calcium ions (Ca), are able to move between cells, but
large molecules, like proteins and DNA, cannot fit through the channels.

• The specificity of the channels ensures that the cells remain independent, but can
quickly and easily transmit signals.

• The transfer of signalling molecules communicates the current state of the cell that
is directly next to the target cell; this allows a group of cells to co-ordinate their
response to a signal that only one of them may have received.
• Paracrine Signalling:

• Signals that act locally between cells that are close together are called paracrine
signals.

• Paracrine signals move by diffusion through the extracellular matrix.

• These types of signals usually elicit quick responses and last for short duration.

• Paracrine ligand molecules are quickly degraded by enzymes or removed by


neighbouring cells.

• Paracrine signalling plays an important role in early development, co-ordinating the


activities of clusters of neighbouring cells.

• One example of paracrine signalling is the transfer of signals across synapses between
nerve cells.
• Synaptic Signalling:

• The cells of the nervous system provide rapid communication with distant cells.
• Their signal molecules, neurotransmitters, do not travel to the distant cells through the
circulatory system like hormones.

• The long, fiber like extensions of nerve cells release neurotransmitters from their tips very
close to the target cells.

• The narrow gap between the two cells is called a chemical synapse.

• Endocrine Signalling:

• Signals from distant cells are called endocrine signals; they originate from endocrine cells.

• In human body, many endocrine cells are located in endocrine glands such as the thyroid
gland, hypothalamus and pituitary gland.

• These types of signals usually produce a slower response, but have a longer lasting effect.
• The ligands released in endocrine signalling are called as hormones, signalling
molecules that are produced in one part of the body, but affect other body regions
some distance away.

• Hormones travel the large distances between endocrine cells and their targe cells via
the bloodstream, which is a relatively slow way to move throughout the body.

• Autocrine signaling:

• Some cells respond to signaling molecules that they themselves produce.

• For example, certain T-lymphocytes respond to antigenic stimulation by synthesizing a


growth factor that drives their own proliferation, thereby increasing the number of
responsive T-lymphocytes and amplifying the immune response.

• Abnormal autocrine signaling frequently contributes to the uncontrolled growth of


cancer cells
Protein Synthesis:
• Transcription: It is the transfer of genetic instructions in DNA to mRNA. During
transcription, a strand of mRNA is made to complement (match) a strand of DNA.

• Transcription begins when the enzyme RNA polymerase binds to a region of a gene called
the promoter sequence.

• This signals the DNA to unwind so the enzyme can “read” the bases of DNA.

• The two strands of DNA are named based on whether they will be used as a template for
RNA or not.

• The strand that is used as a template is called the template strand, or can also be called
the antisense strand.

• The sequence of bases on the opposite strand of DNA is called the non-coding or sense
strand.
• Three types of RNA are made from the DNA template:
• Messenger RNA (m-RNA) directs the synthesis of a protein.
• Ribosomal RNA (r-RNA) joins with ribosomal proteins to make ribosomes.

• Transfer RNA (t-RNA) binds to an amino acid and holds it in place on a ribosome until
it is incorporated (join) into a protein during translation.

• One end of the tRNA carries a specific amino acid, and the opposite end
consists of a triplet of nucleotides called an anticodon.
• Once the DNA has opened, and RNA polymerase has attached, the RNA
polymerase moves along the DNA, adding RNA nucleotides to the growing
mRNA strand.

• The template strand of DNA is used as to create mRNA through


complementary base pairing. Once the mRNA strand is complete, and it
detaches from DNA.

• The result is a strand of mRNA that is nearly identical to the coding strand
DNA – the only difference being that DNA uses the base thymine, and the
mRNA uses uracil in the place of thymine
• This is where RNA polymerase attaches to the DNA. During transcription,
bases pair in a complementary manner:
• The bases cytosine (C), guanine (G), and thymine (T) in the DNA template pair
with guanine, cytosine, and adenine (A), respectively, in the RNA strand.
• However, adenine in the DNA template pairs with uracil (U), not thymine, in RNA
• A U
• T A
• G C
• C G
• A U
• T A
Template DNA base sequence Complementary RNA base sequence
• Translation
• Translation is the second part of the central dogma of molecular biology: RNA → Protein.
• It is the process in which the genetic code in mRNA is read to make a protein.
• After mRNA leaves the nucleus it moves to a ribosomes, which consists of rRNA and
proteins.
• The ribosome reads the sequence of codons, in mRNA and molecules of tRNA bring amino
acids for to the ribosome in the correct sequence.
• Translation occurs in three stages: Initiation, Elongation and Termination.

• Initiation:

• After transcription in the nucleus, the mRNA exits through a nuclear pore and
enters the cytoplasm.

• At the region on the mRNA containing the methylated cap and the start codon,
the small and large subunits of the ribosome bind to the mRNA.

• These are then joined by a tRNA which contains the anticodons matching the
start codon on the mRNA.

• This group of molecues (mRNA, ribosome, tRNA) is called an initiation complex.


• Elongation:

• tRNA keep bringing amino acids to the growing polypeptide according to


complementary base pairing between the codons on the mRNA and the
anticodons on the tRNA.

• As a tRNA moves into the ribosome, its amino acid is transferred to the
growing polypeptide.

• Once this transfer is complete, the tRNA leaves the ribosome, the
ribosome moves one codon length down the mRNA, and a new tRNA
enters with its corresponding amino acid.

• This process repeats and the polypeptide grows.


• Termination:

• At the end of the mRNA coding is a stop codon which will end the elongation
stage.

• The stop codon doesn’t call for a tRNA, but instead for a type of protein called a
release factor, which will cause the entire complex (mRNA, ribosome, tRNA, and
polypeptide) to break apart, releasing all of the components.

• After a polypeptide chain is synthesized, it may undergo additional processing to


form the finished protein.

• Then assemble protein is then released from ribosomes.

• After protein synthesis small and large ribosomes subunits separated.

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