B2, Form and function: Cells

• hydrophilic: polar molecules

• easily form hydrogen bonds with water – molecules get dissolved
• hydrophobic: non-polar molecules
• unable to form hydrogen bond

Overview of membrane structure

• barriers controlling exchange of materials between internal and external environment
• surround cells and organelles
• composed of:
• lipids (phospholipids, glycolipids, sterols)
• proteins
• lipids and some proteins are amphipathic molecules
= hydrophobic and hydrophilic regions
• small amounts of carbohydrates (glycolipids and glycoproteins)

Lipid bilayer
• three major classes of lipids:
• glycolipids
• sterols: such as cholesterol (in animal cells, amphipathic)
• phospholipids: membrane phospholipids most abundant and diverse
• comprise of a backbone (glycerol = a three-carbon alcohol)
• attached to the backbone:
• negatively charged phosphate molecule
• linked to other molecules (choline or serine)
• forming polar, hydrophilic, ‘head’ group
• polar head forms hydrogen bonds with
water
• two non-polar fatty acid chains
• forming hydrophobic ‘tails’
• could be saturated or unsaturated
• unsaturated fatty acids result in kinks in
the tail

R= charged or polar functional group

white circle = Negatively charged phosphate group
middle row = 3 C backbone of glycerol
left tail = fatty acid tail-1 (saturated)
right tail = fatty acid tail-2 (unsaturated)
 • amphipathic: formation of two layers or lipid bilayers
• aqueous environment:
• hydrophobic tails - inward (away from water)
• continuous hydrophobic interior – determines
the permeability of the membrane
• hydrophilic heads – outward (to water)

Lipid bilayers as barriers

• lipid bilayers in almost all biological membranes
• permeability of the membrane:
• depends on the size of molecules and the hydrophilic/hydrophobic nature
• most of the constituents of the cell charged
• membranes form barriers to prevent charged molecules entry

Simple diffusion of molecules

• movement of molecules down a concentration gradient
• from a region with high concentration to a low concentration region
• eventually equilibrium (equal concentration in both regions)
• passive process (no expenditure of energy by cells)
• easy way for molecules to move across the membrane
• spontaneous
• example:
• gas exchange:
• the erythrocytes or red blood cells (RBCs) transport oxygen from the lungs
to the cells of the body. The oxygen diffuses from the oxygen-rich air in the
alveoli down the concentration gradient to blood (erythrocytes) in the
 capillaries surrounding the alveoli. This oxygen is carried to tissues. In
tissues, the oxygen diffuses from erythrocytes where oxygen concentration
is higher to metabolically active cells where oxygen concentration is lower

At the same time, in tissues, carbon dioxide diffuses from the cells where its concentration is
higher to blood where its concentration is lower. The carbon dioxide is then carried to the
lungs. In the lungs, the carbon dioxide diffuses from the blood to the alveoli down the
concentration gradient. Figure 2 illustrates the process. To keep this simple, the reactions that
happen within erythrocytes have not been included here.

• oxygen and carbon dioxide diffuse passively and easily

• However, the hydrophobic nature of the lipid bilayer restricts simple diffusion of most
molecules. Only non-polar molecules like oxygen or carbon dioxide or very small
polar molecules like water or alcohol, can diffuse across membranes.
Membrane proteins and their functions
• differ in location, structure and function
• based on association with the lipid bilayer:
• integral proteins:
• embedded in the lipid bilayer
• difficult to isolate - extraction disrupts the bilayer
• amphipathic:
• hydrophobic regions interact with the hydrophobic interior
• become embedded
• hydrophilic regions interact with the hydrophilic or water
• location:
• most transmembrane proteins (extend across the membrane)
• others only on one side of the bilayer
• peripheral proteins:
• hydrophilic
• interact only with hydrophilic regions of the integral proteins,
sometimes with hydrophilic heads of the phospholipids
• easier to remove from biological membrane
• location: on the surface of the membrane
• both asymmetrically (unevenly) oriented across the membrane

Functions of membrane proteins

• transport proteins: facilitate the movement in and out of the cell

• channel proteins and carrier proteins
• channel proteins = transmembrane proteins forming channels or pores
• carrier proteins = change to transfer molecules
• recognition: help in cell-cell recognition - ‘name tags’
• for the immune system, help distinguish self and non-self cells
• receptors: for chemical signals, create binding sites (for hormones and neurotransmitters)
• binding often triggers a chain of intracellular reactions
• enzymes: show enzymatic activity and catalyse reactions
• glucose-6-phosphatase = membrane-bound enzyme in the endoplasmic reticulum
• help in cell adhesion to cells or the environment
• play a role in cell motility

Osmosis
• diffusion of water from a region of lower solute concentration (and higher water
concentration) to a region with higher solute concentration (and lower water
concentration) through the membrane
• concentration of solutes higher in the cell than outside
• net movement of water into the cell
• eventually concentration same on both sides
• random movement of water molecules continues
• no net movement of water

Aquaporins (AQP)
• discovered in 1992 by Peter Agre
• type of integral channel protein
• structure:
• tetrameric, four monomeric subunits
• each subunit has a water channel - four identical water channels
• water channels lined with hydrophilic side chains (amino acid residues)
• allows passage of water molecules, not ions
• water molecules pass in a single file
• several billion molecules through a single channel at a time
• bidirectional - water can flow in either direction
• depends on concentration gradient

• the volume of water to be transported determines the number of aquaporins

• kindey cells reabsorb water - higher concentration of aquaporins

Facilitated diffusion, active transport in selective permeability of membranes

• facilitated diffusion = movement of molecules down the concentration gradient facilitated
by transport proteins
• by channel proteins: proteins forming channels for passage of polar molecules
• porins: less specific and are larger channels
• ion channels: tiny pores as pathways for ions (Na+, K+)
• highly selective - different channels needed for different ions
• due to:
• binding sites of hydrophilic amino acid side chains
lining the channel are highly ion-specific
• size of the pore as a size filter
• open or close to specific stimuli:
• changes in voltage/voltage-gated channels
• mechanical forces (pressure)
• binding of small molecules to channel proteins or ligand-
gated channels
• gated:
 • open - ions pass through the pore down the concentration
gradient
• closed - pore plugged, preventing passage of the ion

• by carrier proteins: proteins binding to the solute molecules (to be transported)

• change and transfer the molecules to the other side of the membrane
• highly specific for solutes or class of solutes transported
• GLUT = glucose transporter to red blood cell down concentration gradient

Active transport and pump proteins

• active transport = molecules need to be transported from a region of lower concentration
to a region of higher concentration - against their concentration gradient
• needs energy - requires energy-releasing (exergonic) reaction (breakdown of ATP)
• pump proteins = transport proteins for active transport, against concentration gradient
• helps to:
• take up essential nutrients
• take glucose from lumen of intestine to epithelial cells in small intestine
• remove secretory or waste materials from the cell into the extracellular fluid
• maintain right concentrations of ions in the cells
• red blood cells maintain internal sodium and potassium levels
• types: two main types
• direct active transport = energy released used to directly transport molecules
across the cell membrane
• energy derived by hydrolysis of ATP - proteins ATPases/ATPase pumps
• indirect active transport (cotransport) = movement of one solute down its
concentration gradient drives the movement of the second solute against its
concentration gradient

Selectivity in membrane permeability

• simple diffusion based on: physical properties
• the size of the molecules
• hydrophobic or hydrophilic nature
• simple diffusion -permeability of the cell membrane not selective
• facilitated diffusion and active transport involve transport proteins
• selectivity for specific molecules or classes of molecules
• for example:
• gated ion channels like calcium-specific ion channels in muscle
cells regulate the movement of only calcium ions
• carrier proteins highly specific
• GLUT (glucose transporter)
• selective permeability of the membrane due to facilitated diffusion and active transport

Fluid mosaic model

• glycolipids and glycoproteins: most membranes also of small amounts of carbohydrates
 • linked to:
• lipids – forming glycolipids
• proteins – forming glycoproteins
• glycolipids:
• covalent bonding of carbohydrates to lipids
• amphipathic, polar
• restricted to the external surface of the cell membrane
• extend into the extracellular environment
• non-polar lipids embedded in the bilayer
• structure:
• glycoglycerolipids or glycerol-based lipids
• glycosphingolipids or derivatives of sphingosine (cerebrosides and
gangliosides)
• contribute to membrane stability - hydrogen bonds with water surrounding the cell
• glycoproteins:
• covalent bonding of oligosaccharides (short carbohydrate chains) to the protein
• carbohydrate groups of the glycoproteins often stick out into the extracellular
environment
• Functions of glycolipids and glycoproteins:
• cell recognition: glycolipids and glycoproteins as ‘markers’ on the cell surface
• help cells of the body recognise each other
• help cells of the immune system recognise foreign cells
• cell adhesion: both glycolipids and glycoproteins help cells attach and bind to
other cells - form tissues
• cell-adhesion molecules (CAMs)
• cell signalling: receptors for enzymes and other molecules in cell signalling -
receiving and transmitting chemical signals

how the antigens (glycolipids and glycoproteins) present on surface of the red blood cell membranes -
determine blood groups

• glycocalyx: sticky layer formed by the carbohydrate groups of the glycolipids and
glycoproteins
• protrude from the cell surface
 • cell signalling, cell adhesion and cell–cell recognition, protecting the cell surface

Fluid mosaic model

• proposed by Singer and Nicolson in 1972
• framework to understand membrane structures
• describes the arrangement of the lipids and proteins:
• lipid bilayer is fluid – depends on the nature of the fatty acids in the phospholipid
molecules and the amount of cholesterol
• most of lipids and proteins can move laterally (parallel to the membrane)
• the proteins (integral and peripheral) are embedded in the fluid bilayer as a mosaic
• drawing the fluid mosaic model:
Compartmentalisation and organelles
• organelles = structures of cells that perform specific functions
• found in prokaryotic and eukaryotic cells
• membrane-bound only in eukaryotic cells
• example of compartmentalisation in cells
• compartmentalisation: organisation of functions and processes within areas or structures
• separated by plasma membranes
• allows for development of specialised cell structures (chloroplasts, mitochondria)
• cell separates chemical reactions and other cellular processes
• increase the rate of chemical reactions
• for example:
• lysosomes = compartments that break down and recycle waste materials
• macrophages use phagocytic vacuoles - similar to lysosomes
• breakdown of waste requires enzymes
• these enzymes could damage other parts of the cell
• isolating protects the rest of the cell
• use of enzymes in a smaller space
• faster and more efficient
• cell functions of structures found in animal cells:

• nucleus: organelle containing the DNA (histone proteins)

• in chromosomes
• contains nucleolus
• production of ribosomes, a double membrane
• smooth endoplasmic reticulum: organelle producing and storing lipids (steroids)
• detoxification
• rough endoplasmic reticulum: organelle with ribosomes
• producing proteins for use outside the cell
• vesicles: organelle, small sac modifying and assisting the transport of proteins and
other substances
• by fusing with membranes in the cell
• Golgi apparatus: organelle processing and packaging proteins
• then released in Golgi vesicles
• 80S ribosome: organelle - translation (protein synthesis) occurs
• eukaryotic larger, higher mass than 70S prokaryotic ribosomes
• plasma membrane: organelle separating interior from external environment
• controling enter and exit of the cell
• mitochondrion: double membrane-bound organelle
• converting glucose into ATP in cellular respiration
• lysososmes: organelle compartments with enzymes
• break down cellular components
• cytoskeleton: a system of protein fibres (microtubules and microfilaments)
• hold organelles in place, maintains the structure and shape
 • cytoplasm: a water-based jelly-like fluid in the cell
• suspends ions, organic molecules, organelles, and ribosomes
• site of metabolic reactions

• cell functions of structures found in plant cells:

• nucleus: organelle containing the DNA (histone proteins)
• in chromosomes
• contains nucleolus
• production of ribosomes, a double membrane
• smooth endoplasmic reticulum: organelle producing and storing lipids (steroids)
• detoxification
• rough endoplasmic reticulum: organelle with ribosomes
• producing proteins for use outside the cell
• vesicles: organelle, small sac modifying and assisting the transport of proteins and
other substances
• by fusing with membranes in the cell
• Golgi apparatus: organelle processing and packaging proteins
• then released in Golgi vesicles
• 80S ribosome: organelle - translation (protein synthesis) occurs
• eukaryotic larger, higher mass than 70S prokaryotic ribosomes
• plasma membrane: organelle separating interior from external environment
• controlling enter and exit of the cell
• mitochondrion: double membrane-bound organelle
• converting glucose into ATP in cellular respiration
• vacuole: organelle maintaining osmotic balance
• storing substances
 • hydrolytic functions (like lysosomes)
• chloroplasts: double membrane-bound organelles with photosynthesis
• cytoskeleton: a system of protein fibres (microtubules and microfilaments)
• hold organelles in place, maintains the structure and shape
• cytoplasm: a water-based jelly-like fluid in the cell
• suspends ions, organic molecules, organelles, and ribosomes
• site of metabolic reactions
• cell wall: organelle of polysaccharides
• protection against mechanical stresses
• structural support

• not an organelle:
• cytoskeleton: a network of proteins
• shape, movement of molecules around the cell
• not an organelle - not enclosed by a membrane, not in metabolic processes
• cell wall: protection against mechanical stresses, structural support
• not an organelle - not enclosed by a membrane, not in metabolic processes
• cytoplasm: a matrix around structures in the cell
• not a discrete structure with a specific function
• contains all the structures
• ribosomes are not membrane-bound - organelles due to a specific function

Nucleus and cytoplasm

• eukaryotic cell: nucleus
• a double membrane - outer membrane part of the rough endoplasmic reticulum
• compartmentalisation of the nucleus from the cytoplasm:
• nucleus with DNA - regulates genes by transcription of DNA into mRNA
 • cytoplasm responsible for metabolic processes
• translation of mRNA into proteins on the ribosomes
• compartmentalisation allows cytoplasm to send signals to nucleus
• cytoplasm an extracellular signal (hormone/growth factor)
• passed to nucleus to change gene expression
• through increased or decreased transcription
• altering gene expression - produce different amounts/types
of proteins to adjust to different conditions
• in prokaryotic cells: transcription and translation in the cytoplasm
• protein produced soon after the mRNA is finished
• post-transcriptional modification:
• mRNA produced in the nucleus changed by removing pieces of it
• working protein only after this
• compartmentalising the nucleus and the cytoplasm allows
the post-transcriptional change before translation
• is not possible in prokaryotic as no nukleus.

Stem cells
• formation of stem cells:
• fertilisatio: diploid single cell, zygote, divides
• ball of 16-32 cells – morula
• after 5–6 days differentiation into a hollow ball – blastocyst
• outer layer of cells – trophoblast (develop into placenta)
• inner cell mass (ICM) (develop into embryo)

• morphogen gradients:
• different cells for different functions
• cells in one organism identical sequences of DNA, same genes (alleles)
• same genes not expressed at a time
 • determines the type of cell formed
• differentiation = as cells develop to specialised
• embryo: ICM cells identical
• certain cells secrete ‘form-giving’ molecules – morphogens
• outwards from the source - a gradient
• distance of cells from the morphogen-secreting cell:
• cell ‘reads’ its distance in the concentration gradient
• through receptors on its surface
• develops accordingly
• efficient - few genes needed to determine the cell type

• stem cell potency:

• not all stem cells the same ability to differentiate:

Type of stem cell Differentiated cells produced

differentiate into any type of cell including placental cells,

Totipotent stem cell (eight cells of the morula)
give rise to a complete organism

Pluripotent stem cells (embryonic stem cells of the differentiate into all body cells, cannot give rise to a whole
blastocyst) organism

Multipotent stem cells (umbilical cord stem cells) differentiate into a few closely related types of body cell

Unipotent stem cells differentiate into their associated cell type (liver stem cells
only liver cells)

• cells in morula totipotent - differentiate into any cell

• create the embryo, the placenta, the embryonic sac tissues
• blastocyst - less adaptable
• cells in ICM pluripotent -cannot generate organisms, differentiate into three layers
• endoderm (inner layer), mesoderm (middle layer), ectoderm (outer layer)
 • cells in the umbilical cord multipotent - stored for medical use for the child
• cells in bone marrow – rise to all types of blood cells
• used for transplants
• leukaemia/lymphoma
• stem cell niche:

The stem cell niche can be thought of as the microenvironment within the organism in which
the stem cells live and receive their instructions. This environment influences the stem cells
and how they differentiate. There are numerous interactions that can determine what happens
to the stem cells in the niche. There are cell-to-cell interactions and the cell can also interact
with the fluid outside of the cells (extracellular matrix). Signalling molecules can activate, or
prevent genes from transcribing. This leads to some cells being instructed to remain dormant
(inactive) while others are directed to make more of the same kind of stem cell. Still others
become differentiated into another kind of cell.

The stem cell niches in humans that have been studied most are those that make blood, skin,
intestine, brain and muscle cells. Blood stem cells are found in the bone marrow throughout
adulthood. The bone marrow is the soft, spongy centre of most bones and has many blood
vessels associated with it. The bone marrow niche itself is made up of a combination of cells
that make blood cells (haematopoietic) as well as those that are supportive cells. The
supportive cells regulate the function of the ones that generate the blood cells. The
maintenance of the blood cell niche is essential for the constant supply of functional blood
cells throughout the human’s life.
The skin is the largest organ in your body and it will be constantly replaced during your
lifetime. Think about how many new skin cells you have already made since birth! Hair
follicles are a very well-defined and well-studied mammalian cell niche. Hair follicles have
cycles of degeneration, growth and rest so that your body is always covered with mature hair
shafts. The hair follicle stem cells that are responsible for the proliferation of the hair are
found in an area called the ‘bulge’. Other cells in the follicle are responsible for the
breakdown of old hairs and maintaining the rest stage. They work together in an elegant and
choreographed way to achieve a full body of hair at all times.

Cell size
• size variations of human cells:
• 50 to 100 trillion cells in the body
• smallest (RBC) being about 7.5 µm to largest (egg cell) 150 µm
• structure linked to function
• egg cells large and highly specialised – nutrients for development
• sperm small – no nutritional content
• many human cells spherical
• some specialised nerve cells long
• neurons in the sciatic nerve - longest (axons over 1m)
• for communication between the spinal cord and distant parts
• smallest RBCs – erythrocytes
• no nucleus – space for more haemoglobi
• binding oxygen to transport
• highly flexible membrane – can be deformed and spring back

• larger white blood cells - 10 to 20 µm

• nuclei of various shapes - identification
• move in an amoeboid way
• squeeze out of blood vessels into surrounding tissues

• striated muscle fibres - large, multinucleated, extremely long cells

Keeping cells alive

• cells need to grow before division
• control mechanisms - cell surface receptors and growth factors in the surrounding
environment
• maximum size consistent in an organism
• increase in size - room for the organelles and metabolic reactions
• ratio of the volume of the cell with surface area (membrane) – SA:V
• surface area does not increase at the same rate as volume
• larger cell, smaller SA:V ratio
• larger SA:V – easier entry and exit
• balance in large to contain organelles and efficient gas exchange and nutrients