The Dynamic Cell

Units

Characteristics of all cells

A surrounding membrane

cytoplasm - cell contents in thick fluid

Organelles

2 basic types of cells

prokaryotic cells:

All bacteria are prokaryotes

No membrane bound nucleus

Nucleoid = region of DNA concentration

organelles not bound by membranes

eg: Spherical (cocci), Rod - shaped (bacilli), spiral

Eukaryotic cells:

Nucleus bound by membrane

possess many organelles

include fungi, protists, plant, and animal cells

eg: blood cells, neurons, skin cells

why do cells have compartments

Eukaryotic cells are larger than prokaryotic cells

larger cells means greater diffusion distance which can make chemical reaction slower.

what is cell compartmentalisation

• All cells have a plasma membrane.

• Eukaryotic cells have membrane-bound organelles that create separate compartments.

• Each organelle has a specific function.

• Prokaryotes lack membrane-bound organelles and have one main compartment containing the enzymes needed for basic functions.

• Compartmentalisation allows different processes to happen separately and efficiently.

what are the 2 membranes

monolayer and bilayer

Plasma membrane features

composed of phospholipids, cholesterol, proteins and other components

Phospholipids drift within the bilayer

function: regulates what enters and leaves the cell

Cytoplasm components

cytoskeleton (filaments and fibres)

cytosol fluid

organelles (not nucleus)

storage of substances

The nucleus structure and function

Structure: enclosed by a double membrane called nuclear envelope which has pores. Contains nucleolus and chromatin

function: Site of cellular DNA storage, replication and transcription

Ribosomes structure and function

Structure: Composed of RNA and protein

Ribosomes carry out protein synthesis at two locations (in cytosol, free ribosomes or on the outside of endoplasmic reticulum which are bound ribosomes)

Function : protein biosynthesis

Endoplasmic Reticulum

Smooth ER

no ribosomes involved

function = Carbohydrate metabolism, drug metabolism, calcium ion movement

Rough ER

ribosomes involved

Function: involved in the synthesis folding and modification and transport of proteins Site of translation of proteins

Golgi apparatus structure+ function

structure: a stack of flattened membrane bound sacs called cisternae

function - Acts as the packaging and shipping station, packages them into vesicles for transport

what happens in protein trafficking

molecules come in vesicles

vesicles fuse with golgi membrane

molecules may be modified by golgi

molecules go into separate vesicle

vesicle leaves golgi

vesicles combine with plasma membrane to secrete contents

Mitochondria structure and function

Structure - Have their own DNA, Bound by double membrane

Function = Break down organic compounds by aerobic respiration + produces ATP

Lysosomes structure and function

structure: membrane bound vesicles that contain hydrolytic enzymes

Function: Aid in cell renewal, break down old cell parts, involved in intracellular digestion

peroxisomes structure and function

• Structure: Membrane-bound organelles containing enzymes, including catalase.

• Function: Involved in various metabolic reactions, including the synthesis and degradation of hydrogen peroxide (H2O2H2​O2​). They also play roles in lipid synthesis, fatty acid oxidation, and detoxification.

structure and function of cytoskeleton

structure = contains microfilaments (actin) , microtubules( tubulin) and intermediate fibres (neurofilament in neurons)

function: Provide the cell with a certain shape and mechanical stability

Cell movement

Distribution of chromosomes in cell division

acts as an anchor to cells

Microtubules have motor proteins which pull them

cells require communication for:

survival, adaptation and changing environmental conditions

How do Multicellular organisms communicate

they respond to their physical environment and other cells. Cells need to know their correct location within the organism . Stimuli include:

growth factors

Hormones

Cell - matrix

Cell to cell contact

light Photons

Touch

Temperature

what is Signal Transduction

signal transduction is the mechanism by which = a cell detects external stimuli and converts this detection into an internal cellular response usually involving a change in cellular activity.

3 phases of signal Transduction

Receptor - the target cell detects a signal from outside the cell. This occurs when a biochemical signal called a ligand, binds to a specific receptor protein, typically located on the cell surface.

Transduction - binding of ligand to receptor, converts initial signal into a different signal (second messenger) Small non - protein water - soluble molecules that are produced or released in response to ligand binding

Response - The transduced signal triggers a specific cellular activity

key concepts of cell signalling

Specific Molecular Recognition- crucial for interactions between ligands and receptors or between signalling molecules

Molecular switches - proteins can be activated or inactivated through phosphorylation/ dephosphorylation

Signal Amplification - The process by which ligand - receptor interaction can lead to larger cellular response

Types of Cell Communication

Cell Junctions:

Gap Junctions: Channels connecting the cytoplasm of adjacent cells, allowing direct passage of small water soluble ions and molecules. This enables rapid communication between neighboring cells.

Cell - Cell recognition - cells communicate through direct contact between molecules on their surfaces.

Chemically Signalling:

Paracrine signalling - A secreting cell releases signalling molecules that act on nearby target cells

Synaptic signalling - A specialised form of paracrine signalling occurring at synapses between nerve cells. An electrical signal triggers the release of neurotransmitters which diffuse across synaptic cleft to act on the target cell

Autocrine signalling - A cell releases signalling molecules that bind to receptors on its own surface, essentially signalling to itself

Endocrine - Signalling cells release hormones into the bloodstream which act on target cells

Ligands and Types of receptors

ligands - external signal molecules that initiate cell signalling, and bind to receptors. They can be proteins, peptides, lipids, small molecules, or environmental stimuli.

Receptors - cellular proteins, They are typical located on cell surface but can be intracellular

Types of receptors;

Transmembrane - proteins that span the plasma membrane having an extracellular domain

Ion channel linked receptors - ligand binding causes a change that open or closes an ion channel alternating the ion concentrating inside the cell

G protein linked receptors - These receptors are coupled to G proteins. Ligand binding activates the G protein, Which then interacts with other enzymes to relay the signal

Enzymes linked receptors - Ligand binding activates the enzyme activity.

Intracellular receptors - receptors located within the cytoplasm or nucleus so ligands are small

What is Phosphorylation

Phosphorylation is the addition of phosphate group to a protein

This process is catalysed by enzymes called kinases

Dephosphorylation the removal of a phosphate group is catalysed by phosphatases

Phosphorylation often acts a molecular switch altering protein activity

examples of signal amplification

ion channel opening - A ligand binding to an ion channel receptor can cause channel to open allowing large flux of ions across membrane changing ion concentration

Enzymatic Generation of Second Messengers - An activated receptor can activate an enzyme that produces many molecules of a second messenger.

Phosphorylation cascades - A series of kinase activating other kinases in sequence. this can activate multiple downstream kinases leading to signal amplification

in phase 3 of signal transduction what are the proteins called

target (response proteins)

proteins at end of signalling pathway

how is gene expression regulated

Transcription factors can bind to DNA and regulate the expression of specific genes

some transcription factors can activates genes that produce proteins that further amplify signalling or inhibit it

regulation of gene expression can lead to change in proteins

chromosome features

consist of double helix DNA

23 pairs of chromosomes in total 22 pairs of autosomes and 1 pair of sex chromosomes

made of base pairs

sister chromatids

each chromosome after DNA replication contains two identical sister chromatids

sister chromatids are joined together at centromere

centromere is a region of DNA hidden beneath proteins

kinetochores

The kinetochore is a protein complex assembled at centromere

it acts as an attachment site for microtubules in cell division

microtubules and centrioles

microtubules are part of the cytoskeleton and are responsible for various movements within eukaryotic cells

microtubules form mitotic spindle

animal cells have two small organelles called centrioles

centrioles involved in formation of spindle fibres and consist of cylindrical array of 9 microtubules

mitosis vs meiosis

Mitosis

• Division of somatic (body) cells.

• Occurs wherever more cells are needed for growth and repair.

• Produces two new cells that are genetically identical to each other and to the parent cell.

• The process of growth and division is called the cell cycle.

• Results in two diploid (2n2n) daughter cells.

• Chromosome number remains the same in daughter cells.

• Genetic variation does not change.

• Consists of 4 main stages (plus interphase

Meiosis

• Division of germ cells (gametes: sperm and egg cells).

• Occurs for sexual reproduction.

• A human body cell has 46 chromosomes (2n2n), while gametes have 23 chromosomes (1n1n).

• This reduction in chromosome number is why meiosis is sometimes called "reduction division."

• Results in four haploid (1n1n) daughter cells.

• Chromosome number is halved in each daughter cell.

• Genetic variation is increased due to recombination and independent assortment.

• Consists of two successive cell divisions (Meiosis I and Meiosis II), with 8 stages in total (plus interphase).

mitotic cells in the adult human body

eg:

hair follicle cells

fibroblasts

stem cells

skin cells

heart endothelial cells

intestinal epithelial cells

what is hayflick limit

normal somatic cells have limited number of times they can divide known as the hayflick limit. This is around 50 population doublings

mitosis and cancer cells

normal cells have checkpoints that regulate cell division and stop if DNA is damaged

Cancer cells bypass these checkpoints leading to uncontrolled cell division

mitosis and stem cells

2 types of division ]

Symmetric division - produces two identical daughter cells

Asymmetric division - Produces one daughter cell that remains a stem cell and another daughter cell that differentiates into a cell type

cell cycle and mitosis

• Interphase: The longest phase, where the cell grows and replicates its DNA.

  • G1 Phase: Cell growth and preparation for DNA synthesis.

  • S Phase: DNA replication occurs. The cell goes from a diploid (2n2n) state to a tetraploid (4n4n) state in terms of DNA content.

  • G2 Phase: Further growth and preparation for mitosis.

• M Phase (Mitosis): The period of nuclear division.

  • Prophase: Chromosomes condense and become visible, each consisting of two sister chromatids. The nuclear envelope disintegrates, and the mitotic spindle begins to form.

  • Metaphase: Chromosomes align at the metaphase plate (equator of the cell), attached to spindle fibers. Homologous chromosomes do not associate.

  • Anaphase: Sister chromatids separate and are pulled to opposite poles of the cell.

  • Telophase: Chromosomes decondense, nuclear envelopes reform around the two sets of chromosomes, and the spindle fibers disappear.

• Cytokinesis: The division of the cytoplasm, which usually overlaps with telophase, resulting in two distinct daughter cells.

cell cycle checkpointsG₁ Checkpoint (Restriction Point):

• G₁ Checkpoint (Restriction Point):

  • Question: Is the environment favorable for cell division (e.g., sufficient nutrients, growth factors)?

  • Outcome: If favorable, the cell enters the cell cycle and proceeds to S phase.

• G₂/M Checkpoint:

  • Question: Is all DNA replicated, and is it free of damage?

  • Outcome: If conditions are met, the cell enters mitosis.

• Metaphase-to-Anaphase Transition (Spindle Checkpoint):

meiosis 1

• Prophase 1: Homologous chromosomes pair up (synapsis) to form tetrads. Crossing over occurs, leading to genetic recombination and increased genetic diversity.

• Metaphase 1: Homologous pairs of chromosomes line up at the metaphase plate. Spindle fibers attach to the centromeres.

• Anaphase 1: Homologous chromosomes separate and move to opposite poles. Sister chromatids remain attached.

• Telophase 1: The cytoplasm divides, forming two haploid (1n1n) daughter cells. Each chromosome still consists of two sister chromatids. genetically different

meiosis 2

• Prophase 2: Spindle fibers form in each of the two daughter cells.

• Metaphase 2: Chromosomes align at the metaphase plate in each cell.

• Anaphase 2: Centromeres separate, and sister chromatids (now individual chromosomes) move to opposite poles.

• Telophase 2 and Cytokinesis: Nuclei reform at opposite poles, and the cytoplasm divides. This results in four genetically unique haploid (1n1n) daughter cells.

why we need meiosis

For sexual reproduction

Fertilisation

Genetic diversity through crossing over and independent assortment

consequences of Non Disjunction in meiosis

Non disjunction - failure of homologous chromosomes or sister chromatids to separate properly during meiosis

Trisomy - if non disjunction occurs gametes may have extra chromosome eg: down syndrome

monosomy - other gametes may be missing a chromosome

errors in meiosis

chromosome abnormalities, deletions, translocation

cell fates can be broadly categorised into

division - increasing in number

survival - continuing to exist

cell death - undergoing a programmed cell death

differentiation - becoming a specialised cell type

key cell survival pathway IGF1

insulin like growth factor pathway is crucial cell survival pathway

IGF1 binds to IGF - 1 receptor which activates phosphoinositide 3 kinase. that then activates Akt (protein kinase b)

Akt inactivates proteins that promote cell death and thus promotes cell survival

what is Apoptosis

programmed cell death

Characteristics:

cell shrinkage

chromatin condensation

disintegration of organelles

what is cell growth and proliferation

cell growth:

involves an increase in cell size and increase in cell number

synthesis of new proteins, membrane liquids

increase number of organelles

may involve replication of DNA

Proliferation:

Involves replication of DNA and division to produce two cells

Usually follows from a cell growth phase

Positive and negative Growth/Proliferation signals

Growth Stimulating Pathway - Growth factors bind to receptors, activate transcription factors. These transcription factors stimulate the cell cycle

Growth Inhibiting Pathway - Growth inhibiting factors can also signal through receptors

what is differentiation

the process by which cells become specialised cell types

usually but not always involves them ceasing to proliferate

deregulation of cell fate mechanisms and cancer

self suffciency growth signals

insensitivity to anti - growth signals

Evading Apoptosis

Limited Replicative Potential

cell death important roles:

embryogenesis and fetal development

damage control

homeostasis

malignant cancer cell control

immune system regulation

2 types of primary cell death

1. Necrosis - uncontrolled cell death process often associated with disease or injury

2. Apoptosis - programmed cell death essential for normal health and development

Importance of Apoptosis

embryonic development - essential for tissue sculpting

immune system - eliminates virus infected cells

homeostasis - balances cell proliferation and removes aged or damaged cells

Cancer treatment - radiotherapy and chemotherapy drugs induce apoptosis in cancer cells

2 main pathways that trigger apoptosis

1. Extrinsic pathway (Receptor mediated) - Triggered by external signals binding to cell surface death receptors

2. Intrinsic Pathway (Mitochondria Mediated) Triggered by internal cellular stress or damage

stages of apoptosis

1. Death signal (intrinsic or extrinsic)

2. Commitment to die (reversible)

3. Execution - irreversible stage

4. Dying cell - cell shrinkage and condensed

5. Phagocytosis -Apoptotic bodies are engulfed by macrophages and neighbouring cells

what are caspases ( The Chief Executioners)

central to apoptosis

They exist as inactive pro enzymes

Activation occurs through cleavage

Activated caspases can trigger a cascade

Extrinsic pathway explained

Begins with ligands binding to death receptors on cell surface

• Ligand binding leads to the recruitment of adaptor proteins eg: procaspase-8 to the receptor.

allows activation of caspase 8

this activates effector caspases

Intrinsic Pathway can be activated by:

• DNA damage

• UV radiation

• Viral infection

• Free radical damage

• Absence of survival signals

The role of mitochondria intrinsic pathway

Cytochrome C release - under stress, pores form in outer mitochondrial membrane releasing cytochrome c from intermembrane space into the cytosol

Apoptosome formation - in cytosol, cytochrome c binds to other proteins to form multi protein complex called apoptosome

caspase 9 activation - apoptosome recruits pro caspase 9 this activates effector caspases

Hallmarks (characteristics) of Apoptosis

• Cell shrinkage

• Maintenance of organellar integrity (initially)

• Maintenance of ATP levels

• Maintenance of ion homeostasis

• Membrane surface blebbing

• Nuclear chromatin condensation and fragmentation

• Requires the synthesis of death effector proteins (active process)

• Can be prevented by blocking steps in the death cascade

• Does not adversely affect neighboring cells

• No inflammation

causes of necrosis

• infection (pathogens)

• Direct toxic threats (chemicals, toxins)

• Extreme temperatures (freezing, burns)

• Excitotoxicity (excessive neurotransmitter stimulation)

• Trauma (mechanical injury)

• Hypoxia (lack of oxygen)

• Ischemia (lack of blood flow)

Necrosis process

1. Insult - trauma, toxic, chemicals, heat

2. loss of homeostasis - loses ability to regulate internal environment

3. ion influx and swelling

4. Enzyme activation and damage

5. production of toxic compounds

6. cell death

7. Inflammation - leakage of cellular contents trigger inflammatory response

Hallmarks (characteristics) of Necr

• Cell swelling

• Organellar swelling and damage

• Depletion of ATP

• Loss of ion homeostasis

• Membrane rupture

• Nuclear lysis

• Cessation of protein synthesis

• Irreversible process

• Promotes the death of neighboring cells

• Causes inflammation

apoptosis vs necrosis

what is necroptosis

Necroptosis is a more recently identified form of programmed cell death that shares features of both apoptosis and necrosis.

• It is a regulated, controlled form of necrosis.

• It involves molecular "switches" that allow cells to decide between apoptosis and necroptosis.

in tissues cell can be connected together via:

cell to cell

cell to extracellularmatrix

microfilaments (actin filaments)

functions

Determine cell shape

essential for cell movement

involved in muscle contraction

role in cytokinesis (cell division)

intermediate filaments

composition

structure

function

composition: diverse group of proteins

structure: appear as rope like fibres

functions: provide mechanical strength and resilience to cells and tissues. Helps connect cells together, maintain cell shape

Microtubules

structure

functions

structure - hollow cylinders

function: position organelles within cells, contribute to cell shape and movement, crucial for forming mitotic spindle during cell division, internal transport system for vesicles and organelles

what is cell migration process

1. Protrusion - actin filaments polymerise, pushing cell membrane forward

2. adhesion - adhesion sites form between cell and extracellular matrix

3. retraction - myosin motors pull cell body forward and old adhesion sites disassemble, actin enables rapid shape changes and directional movement in response to chemical changes

Extracellularmatrix components

Long protein fibres:

Collagen - most abundant protein in human body, high temsile strength and crucial for bones

elastin - provides elasticity to tissues to stretch and recoil

proteoglycans - long chain sugar molecules, lubricate ecm

specialised molecules:

fibronectin - a large glycoprotein receptor that binds to cell surface receptors

Extracellularmatrix functions

provides structural and mechanical support to tissue

acts as a scaffold influencing cell behaviour and differentiation and survival

forms basement membranes

describe all the cell - cell connections

tight junctions - seal adjacent cells together forming a barrier. They provide mechanical strength

adherens junctions - provide mechanical strength and involved in cell - cell adhesion

desmosomes - strong adhesion points that resist mechanical stress, anchor cells together

gap junctions - channels that directly connect the cytoplasm of adjacent cells allowing passage of small molecules and ions

describe all cell - ECM connections

focal adhesions - sites where cells attach to the ECM

Hemidesmosomes - anchor cells to the basement membrane

Role of cytoskeleton

Mechanical Strength

coordinated action

cellular behaviour - differentiation, proliferation, migration

cell movement

what diseases can occur in:

cytoskeleton?

cell - cell interactions?

ECM?

Neurodegenerative diseases

autoimmune diseases

chronic inflammation

what other movement is there outside ECM

motor proteins attached to microtubules propel cell forward -eg: sperm

substances move along cell surface eg: cilia