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Cellular Level of Organization
Cellular Level of Organization
• 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.
• 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.
• Transport proteins: Many membrane proteins form channels that facilitate the transport of
water (aquaporins), ions, and nutrients like sugars and amino acids.
•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:
• Functions:
• 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).
• 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.
• 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.
• Functions:
• Function:
• 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.
• Nucleoli degenerate during cell division and reorganize once new cells are
formed.
• 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.
• Functions:
• 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.
• 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.
• 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.
• 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.
• 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- 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).
• 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.
• 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.
• 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).
• 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.
• 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.
• 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.
• 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.
• These types of signals usually elicit quick responses and last for short duration.
• 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:
• 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 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.
• 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.
• 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.