CELL MEMBRANE - Digestive enzymes then leak out and damage

nearby tissues
• Highly fluid, dynamic (exhibits rapid turnover
and lateral diffusion)
• Composed of proteins, lipids, and carbohydrates
• Asymmetric, sheet-like structures with inner and
outer surfaces
• Viscous, plastic structures
o E.g. RBC that have to pass through sinusoid
should be pliable 4. Cancer metastasis
• thermodynamically stable and metabolically - Less adhesive property of cell membrane causes
active cancel cells to circulate and metastasize
• noncovalent assemblies composed of lipids, 5. Cystic fibrosis
proteins, and carbohydrates - Defective CFTR causes decreased secretion of Cl-
• Normal cellular functions depend on normal ions which in turn causes an influx of Na+ ions
membranes - Water enters the cell through osmosis which
dehydrates the mucus membrane
- Sticky mucus traps bacteria in the lungs
DISRUPTION OF CELL MEMBRANE STRUCTURE
= DISEASE

WHY STUDY THE CELL MEMBRANE

1. Familial hypercholesterolemia
- Lack of LDL receptors on cell membrane keeps
LDL in the bloodstream; thus, high blood
cholesterol

CHARACTERISTIC OF CELL MEMBRANE

2. Hereditary spherocytosis
- RBC cell membranes are normally small to allow
easy entry into small passages
- Spherocytosis – lack in protein assembly
(spectrin & ankyrin) resulting into spherical cells
➢ Asymmetric
➢ Viscous and plastic
➢ Dynamic (rapid turnover; ever-changing)
➢ Thermodynamically stable; metabolically active
➢ Non-covalent assemblies composed of lipids,
proteins, and carbohydrates

INSIDE-OUTSIDE SYMMETRY

• irregular distribution of proteins: transmembrane

and peripheral proteins
• external location of carbohydrates
• specific enzymes exhibit specificity of location
• phospholipids (choline containing are external while
amino acid containing are in the inner leaflet)
3. Acute pancreatitis
- Inflammation of pancreatic cells cause of
disruption of cell membrane

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REGIONAL ASSYMETRY o Replicate
o Perform special functions
• Villous border (e.g. villi found in the small intestine,
microvilli found in the ears and fallopian tubes) EXTRACELLULAR FLUID (ECF)
• Gap junctions
• 1/3 of TBW
• Tight junctions
• 2 compartments: PLASMA and INTERSTITIAL FLUID
Establishing lipid symmetry • Delivery system of nutrients, ions, oxygen, and
hormones to cells
1. Using translocases/flippases
• Removes waste products from the cells
• Enzymes for phospholipid synthesis are at the
cytoplasmic side of the microsomal membrane
vesicles
• Translocases or flippases transfer phospholipid
from inner to outer leaflet
2. Preference of specific proteins for individual
phospholipid
3. Phospholipid exchange proteins (PEP): reorganize
certain phospholipids and transfer them from the INTRACELLULAR EXTRACELLULAR
ER to other parts of the cell (High in) (High in)
K+ Na+
FUNCTIONAL PROPERTIES Mg 2+ Ca 2+
Proteins Glucose
1. Cell individuality – separates cell from other cell Major anion: Phosphate Major cation: Chloride
2. Selective permeability -aided by carriers and
channels, allowing exchange between cell and the
MEMBRANE LIPIDS
environment
3. Cell-cell interaction and adhesion – interactions thru
• amphipathic (have both hydrophobic and
hormone-receptor complex, adhesion of cells to
hydrophilic regions)
basement membrane and other cells
• Basic structure of the cell membrane
4. Transmembrane signaling – thru signal transduction
• Forms a lipid bilayer that is impermeable to
mechanism
water-soluble molecules which results to the
5. Compartmentalization (forms specialized
need for channels and transporters
compartments – organelles)
• Lipid bilayers are formed by self-assembly driven
6. Enzyme localization
by hydrophobic effect
7. Excitation-response coupling
8. Energy transduction

In cancer, cell to cell adhesion is lost,

which leads to metastasis

MAJOR BODY COMPARTMENTS

Body = 60 water FATTY ACIDS

INTRACELLLULAR FLUID (ICF) • Saturated with straight tails (resulting to more rigid
cell membranes)
• 2/3 of TBW
• Unsaturated fatty acids have kinked tails (more fluid
• Provides environment for the cell to
membranes)
o Synthesize, store, and utilize energy
o Repair itself

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 3 MAJOR MEMBRANE LIPIDS
1. PHOSPHOLIPIDS – lipids with phosphate groups
A. Phosphoglycerides
• Most common
• Consists of a glycerol backbone to which area
attached two fatty acids in ester linkage and
phosphorylated alcohol like ethanolamine,
choline, serine, glycerol, or inositol
• Fatty acids are even-numbered (16-18 C
atoms) which could be saturated or
unsaturated
• Simplest is phosphatidic acid
• Inositols are found internally and function for
signal
B. Sphingomyelin
• Second major class
• Sphingosine backbone instead of glycerol
• The fatty acid is attached by an amide link to
the amino group of sphingosine -- ceramide
• Hydroxyl group of sphingosine is esterified to
phosphorylcholine
• Sphingomyelin is prominent in myelin sheath
because they are important for saltatory
conduction at node of Ranvier
• Sphingomyelin is prominent in myelin sheath
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2. GLYCOSPHONGOLIPIDS – sugar containing lipids built
on a backbone of ceramide
• Cerebrosides – ceramide + sugar
(monosaccharide)
• Gangliosides – ceramide + more sugar
(oligosaccharide)
• Both are structures found in CNS
3. STEROLS
• Most common is cholesterol
• Modifies membrane fluidity
• Derived from acetyl coA
• Intercalates between phospholipids in cell
membrane
• amphipathic
• “moderator molecule”
• High temp – limits disorder and fluifity
(condensing effect)
• Low temp – increases fluidity by interfering with
the interactions of hydrocarbon tails of fatty
acids (induces disorder)
MEMBRANE PROTEINS
• Major functional molecules of membranes
• Proteins are for specific tasks in the membrane
• Amphipathic: hydrophilic regions are protruding
at the inside and outside faces of the membrane
but connected by a hydrophobic region
traversing the hydrophobic core of the bilayer
• Different membranes have varying protein
compositions. Thus, important functions of a cell
are determined by its proteins
• Functions of membrane proteins:
o Enzymes
o Pumps, channels, carriers
o Antigens
o Receptors
o Structural proteins
• Types of membrane proteins:
o Integral proteins
▪ Interact extensively with phospholipids
▪ Require detergents for solubilization
 ▪ Amphipathic, globular and, in certain
proteins, spans the bilayer several times
(e.g. G proteins)
▪ Asymmetrically distributed in cell
membrane
▪ The orientation was conferred by the
time of insertion to the bilayer during
synthesis in the ER
▪ Most membrane proteins fall under
integral proteins
▪ Usually channels and carrier
o Peripheral proteins
▪ Do not interact directly with
phospholipid (do not require detergents
for release)
▪ Weakly bound to hydrophilic regions
▪ Attached to integral protein
▪ Usually found inside the cell
▪ E.g. Ankyrin is bound to integral protein
Band 3; spectrin is in turn bound to
ankyrin
MEMBRANE CARBOHYDRATES
• Occur in association with lipids or proteins
• Most prominent in the cell membrane are:
o Glycolipids
o Glycoproteins
• Mostly found on the external membrane surface
• Functions:
o Receptors
o Antigens
• Confers negative charge to cell (as glycocalyx)
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FLUID MOSAIC MODEL
• Universally accepted description of membrane
structure coined by Singer and Nicolson (1972)
• Lipid bi-layer with embedded proteins
(trilaminar under electron microscope)
• “Icebergs” (proteins) floating in a “sea” of
phospholipids
o These proteins and lipids are capable of
lateral diffusion, which means that they can
move from one part of the cell to another
• Membrane lipids = fluid part
• Membrane proteins = mosaic part
• Membranes undergo changes from stiff (gel or
crystalline) to fluid state
• Proteins and lipids undergo rapid redistribution
(“lateral diffusion”)
MEMBRANE FLUIDITY
• Critical to its function; some cells have acquired
the ability to vary the fluidity of their membranes
as needed
Factors that affect membrane fluidity:
• Lipid composition
o Longer and more saturated fatty acid chains
exhibit higher transition temperature
(increases membrane solidity)
o Unsaturated fatty acids increase membrane
fluidity; create a kink (bend)
• Prevents fatty acids from packing together as
tightly
• Decreases the melting temperature (increasing
the fluidity) of the membrane
• Membrane with more saturate fatty acid has a
higher transition temperature. The membrane is
more compact so a higher temperature is
needed to disrupt the order of the lipids
 • Temperature
• Transition Temperature (Tm) – temp at
which structure undergoes transition from
ordered to disordered state
o High temp – more fluid
o Low temp – hydrophobic side chains
become aligned – stiff structure
• Cholesterol
• Moderator molecule
• T above Tm, decreased fluidity due to its
rigid structure (condensing effect)
• T below Tm, increasing fluidity (induces
disorder)
oIn a polar environment, the hydrophilic region
is facing the solution and the hydrophobic
regions are situated in the interior of the
micelle.
o In a non polar environment, the hydrophilic
region is found in the interior while the
hydrophobic region faces the solution (inverse
micelle)
• Used in detergents
• Single-layer unlike cell membrane

Importance of Membrane Fluidity

• it affects protein mobility and transport of

substances across the membrane
• Permeability to water and other hydrophilic
molecule increases
• Lateral mobility of integral proteins increases
• Clinical application of micelles
• Especially for transport and receptor proteins
• Increase in membrane fluidity allows:
o more permeability to water and other
hydrophilic molecules
o lateral mobility of integral proteins, which
includes receptor proteins and transport
proteins
o Emulsification of fats: bile acids associate with
products of lipid digestion to form micelles. Bile
breaks down fat globules into smaller pieces as
micelles, increasing the surface area of the fat
globule for easier digestion by enzymes
o Bile acids – forms micelles that assist in the
digestion and absorption of fat and vitamins A,
D, E, K

Structure of a micelle

Lonophores

• Synthesized in microbes
• Shuttles for ion movement
• Hydrophilic center, hydrophobic peripheral
• Diffusion/hollow channels are formed
ARTIFICIAL MEMBRANES & OTHER SPECIAL
MEMBRANE STRUCTURES

MICELLES
• Small aggregates of amphipathic molecules that
form a monolayer with
o Hydrophobic regions - shielded from H2O
hydrophilic regions – immersed in H2O
o The arrangement of the two regions depends
on the chemical environment where the micelle
is located

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 LIPOSOMES
GAP JUNCTIONS
• Artificial membrane vesicle surrounded by a lipid
• Low resistance connections between the cells
bilayer
• Connexon – functional unit of gap junction
• Consists of phospholipids that can be natural or
• The alignment of a connexon of one cell with the
synthetic in origin
connexon of other cell forms a channel
• Uses:
• Function:
o Lipid content can be varied for the examination
o Allows for the movement of ions and small
of varying lipid composition on certain
molecules between cells
functions (i.e. transport)
o Couples adjacent cells electrically
o Study of factors that affect protein and enzyme
o Gap junctions are commonly found in smooth
function
muscular tissue because movements have to
o May be used for specific drug delivery and gene
be synchronized – in heart muscles, they are
therapy
known as syncytium (pumping of the heart,
▪ Drug delivery: protect drug from enzymatic
peristalsis)
degradation
▪ Involved in and enhances signal
transduction by clustering the elements in
cholesterol, sphingolipids, and proteins

TIGHT JUNCTIONS
• Located below the apical surface of epithelial
cells
• Prevent diffusion of macromolecules between
them
• Composed of proteins, occludin, claudins
• Route for paracellular transport – Na+-K+ ATPase
pump which is found in the basolateral surface,
maintains the high Na+ in the blood. When Na+
enters the cell, water goes with Na+. thus, water
is able to enter the cell via paracellular transport)
• Means of attachment; physical connection
between cells

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 LIPID RAFTS
• Dynamic areas of the exoplasmic leaflet of the
lipid bilayer enriched in cholesterol,
sphingolipids, and proteins
• Involved in and enhances signal transduction by
clustering the elements by signaling systems
• Caveolae – special type of lipid raft
o Mostly found in the smooth muscle cells
o Store Ca2+ inside and release them into
sarcolemma when needed (muscle
contraction)
(eg G-protein coupled receptor, tyrosine
kinase receptor)
o Intracellular
▪ In the cytoplasm or at the nucleus
(intracellular receptors) – regulates gene
expression by affecting the rate
transcription; for lipid soluble messengers
▪ No secondary messengers
• Attachment of one hormone to a receptor
results to multiple effect since signal is amplified
• Importance
o Cell membrane is selective – prevents
leakage of essential substances and free
entry of foreign substances
o Cell membrane receives and transmits
signals to and from other cells

SIGNAL TRANSDUCTION TRANSPORT SYSTEM

• Signal transmission across the membranes • Transport system according to Direction of

• Biochemical signals from hormones, Movement
neurotransmitters bind to receptors in cell 1. UNIPORT
membrane • Moves one type of substance
o Hormones and neurotransmitter cannot bidirectionally (i.e. glucose transported
enter the cell, they can only attach to into cell through influence of insulin)
receptors found in the cell membrane 2. COTRANSPORT
• Through the generation of signaling molecules • SYMPORT – moves two solutes in the
the information is transmitted to the cytoplasm same direction (ie Glucose transported
• Signaling molecules: together with Na+)
o Cyclic nucleotides • ANTIPORT – moves two solutes in
o Calcium opposite direction (ie Na+ (in) and Ca++
o Diacylglycerol or H+ (out) and Cl-HCO3 exchanger in
o Phosphoinositides RBC membrane)
• Receptors can be found:
o Extracellular
▪ Hormones and neurotransmitters cannot
enter the cell, thus only attach to receptors
found in the cell membrane
▪ At the cell surface (plasma membrane
receptors) – generates secondary
messengers; for lipid insoluble messenger

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PASSIVE TRANSPORT
• From high concentration to a lower
concentration without the expense of energy
• Some molecules can passively traverse the
bilayer down electrochemical gradients by
simple diffusion or by facilitated diffusion
• Unlike active transport, passive transport does
not require energy because it does not
constitute movement against an electrochemical
gradient
SIMPLE DIFFUSION
• Transport across the membrane down an
electrochemical gradient
• No need for energy
• Passive flow of a solute from a higher
concentration due to random thermal
movement
• The difference between facilitated diffusion (FD)
is that FD is mediated by a specific protein
transporter
• Movement via simple diffusion is limited by:
o Thermal agitation of that specific molecule
o Concentration gradient across the
membrane
o Solubility of that solute (permeability
coefficient) in the hydrophobic core of the
membrane bilayer
• Involves kinetic energy of molecules
Factors affecting simple diffusion:
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1. Concentration across the membrane – solutes
move from high to low concentration
2. Electrical potential across the membrane – solutes
move toward the solution that has the opposite
charge (the inside of the cell is usually negative)
3. Permeability coefficient of the substance for the
membrane (lipid solubility)
4. Hydrostatic pressure gradient across the membrane
– higher pressure will increase the rate and force of
the collision between the molecules and the
membrane
5. Thickness of membrane – the thinner the
membrane the greater the rate of diffusion
6. Temperature – increased temperature will increase
particle motion and thus increase the frequency of
collisions between external particles and the
membrane
7. Distance – increased distance= decreased rate of
collision
8. Number of channels – increased number of
channels = increased rate of diffusion
ION CHANNELS
• For water soluble substances (ions) that cannot just
simply permeate the membrane
• Permeability depends upon:
o Size
o Extent of hydration
o Charge density of the ion
o There are specific channels for each ion
o Activity of some channels are regulated by
neurotransmitters
• Function can be impaired by disease/mutations
• Channels can be “gated”
• Specific channels for Na+, K+, Ca2+, and Cl- have
been identified
• Membranes of nerve cells contain ion channels
that are responsible for the generation of action
potential
 • Activity of some ion channels is controlled by 3. Carriers exhibit maximum transport (Vmax) or
neurotransmitters saturability
4. There is binding constant (Km) for the solute

The rate of facilitated diffusion, a uniport

Ion Channel Gating system, can be saturated. Many facilitated
diffusion systems are stereospecific are
1. Voltage gating
driven by the transmembrane
• Channels open or close in response to changes in
electrochemical gradient.
membrane potential
• E.g sodium channels
2. Ligand gating
• A specific molecule or chemical binds to a receptor
which opens the channel
• E.g use of neurotransmitters like Ach
3. Mechanical gating
• Channel respond to mechanical stimuli
• pressure and touch
The rate of movement in passive diffusion is
AQUAPORINS directly proportionate to solute
concentration. The process is saturable,
• Water channels found in certain cells : RBC, distal however, when carriers are involved (carrier
tubules and collecting ducts of renal nephrons – mediated diffusion). The concentration at
• Tetrameric membrane proteins half maximal velocity is equal to the binding
• Distinct aquaporins : AP-1 to AP- 5 constant (Km) of the carrier for the solute.
• Mutation in AP-2 is the cause of nephrogenic (Vmax, maximal rate)
diabetes insipidus

FACILITATED DIFFUSION

• A uniport system
• Explained by the “PING PONG” mechanism
o Ping state = carrier is exposed to high
concentrations of solute. Molecules of the solute
bind to specific sites on the carrier protein
o Pong state = carrier is exposed to a lower
CARRIER MEDIATED TRANSPORT concentration of solute. Solute is discharged
Facilitated diffusion and active transport are similar in (released from binding) where it goes to the side
the following: of the membrane that favors the new

1. Involve carrier proteins

2. Show specifically for ions, sugars, and amino
acids

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 equilibrium • Is the transport of solute across a membrane in
the direction of increasing concentration, and
The Na+ K+ ATPase of the plasma membrane is
a key enzyme in regulating intracellular
concentration of Na+ K+

• In the ping state, the conformation of the protein

exposes the binding site to high concentration of
solute, the molecules pf the solute bind to specific
sites on the carrier protein
• The binding will cause a conformational change
(pong state) on the carrier protein which exposes
the binding site to the side of lower solute
concentration, the solute is discharged from the
Na+ K+ ATPase pump moves three Na+ ions
carrier to achieve equilibrium
from the inside of the cell to the outside and
• Empty carrier reverts back to original conformation brings two K+ ions from the outside to the
(ping state again) completing the cycle inside for every molecule of ATP hydrolyzed to
ADP by membrane associated ATPase (Mg2+ is
The rate at which solutes enter a cell by facilitated
a cofactor)
diffusion is determined by:
Ouabain and digitalis, inhibit the Na+ K+
1. Concentration gradient across membrane ATPase by binding to the extracellular domain.
2. Amount of carrier available (key control step)
3. Rapidity of solute-carrier interaction thus requires energy (frequently derived from the
4. Rapidity of conformational change for both the hydrolysis of ATP); a specific transporter (pump)
loaded and unloaded carrier is involved
5. Presence of certain hormones : insulin, GH, and ▪ Secondary active transport – “piggy-back”
glucocorticoids • Energy is from electrochemical gradient
generated by primary active transport
Hormones can regulate facilitated diffusion by changing
• Mechanism for oral rehydration solution
the number of transporters available (ie insulin increases
glucose transport in fat and muscke by recruiting glucose
transports (GLUT) from an intracellular reservoir)

ACTIVE TRANSPORT
- Movement of molecules across the membrane from
low to high concentration through specialized
protein channels with the use of energy
▪ Primary active transport
• Requires energy from light, electron movement
or ATP hydrolysis
• Energy for this process represents 30-40 of
energy expenditure of the cell
• E.g. Na+ K+ ATPase OSMOSIS
• The net flow of solvent across a semipermeable
membrane from an area of LOWER SOLUTE
CONCENTRATION to an area of HIGHER SOLUTE
CONCENTRATION
• Due to a semipermeable membrane that only allows
the solvent to pass

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• Affected by osmotic pressure
Osmotic Pressure
• Minimum pressure required to negate or reverse
osmosis
• Force or pressure is applied on the side of the
membrane with higher solute concentration to push
the solvent back to the area with low solute
concentration
• Determined by the number of particles per unit
volume of fluid
• Volume may increase or decrease to accommodate
equilibrium if non-penetrating solute is concerned
Water follows Na+
- maintains cell volume
- every action potential that is generated
disrupts the gradient; this movement helps
maintain the normal environment
CELLULAR TRANSPORT OF MACROMOLECULES
• Involves vesicle formation with or from the plasma
membrane (PM)
• Two process:
o Endocytosis
o Exocytosis
ENDOCYTOSIS
• Uptake and hydrolysis of molecules yielding
nutrients
• Provides a mechanism for regulating the content of
certain membrane component (eg hormone
receptors)
• Responsible for DNA transfection (entry of DNA into
the cell)
o DNA from one cell transfecting a different cell,
altering the latter’s function and phenotype
o Uses Ca2+ (Ca2+ stimulates endocytosis and
precipitates DNA, making NDA a better object for
endocytosis)
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• Involves macromolecules: proteins,
polysaccharides, and polynucleotides
• Requires the following:
o Energy
o Ca2+
o Contractile elements/proteins (microfilament
system)
• Types
o PINOCYTOSIS
▪ Cellular uptake of fluid and fluid content
▪ FLUID-PHASE PINOCYTOSIS
➢ Also called “cell drinking”
➢ Causes invaginations in the plasma
membrane resulting to formation of
vesicles
➢ Is a nonselective process – no requirements
➢ Uptake of a solute through small vesicle
formation that is proportionate to its
concentration in the ECF
➢ Is an active process (requires ATP)
▪ ABSORPTIVE PINOCYTOSIS
➢ Is a receptor-mediated selective process for
the uptake of macromolecules
➢ High affinity receptors permit the selective
concentration of ligands from the medium,
minimize the uptake of fluid or soluble
unbound macromolecules, and increase the
rate at which specific molecules enter the
cell
➢ Involves clathrin-coated pits
- Cell membrane with invagination/pits
where the receptors for a particular
molecule can be found
- Underneath the pits in the cystosolic side
is a contractile protein called clathrin
➢ May be a mechanism through which certain
viruses enter the cell causing disease
- HIV – affects T cells
- Hepatitis – live cells
 - Poliomyelitis – motor neurons
➢ eg LDL receptors – cholesterol
➢ receptors that can recognize carbohydrate
moieties – extracellular glycoproteins
- galactosyl receptors – asialoglycoproteins
- mannose 6-phosphate moiety receptors-
acid hydrolases
o dynamin – binds and hydrolyzes GTP for the
pinching off of clathrin-coated vesicles from
the cell surface
Fate of the vesicles after the invagination
• acted upon by lysosomes producing primary
phagolysosomes that will eventually become
secondary phagolysosomes (contain hydrolytic
enzymes) which will digest the contents of the
vesicles
• digested materials will be converted to amino acids,
simple sugars and nucleotides – transported out of
the vesicles to be used by the cell

What happen to the PM after Endocytosis?

• PM getting less and less

o endocytosed large materials in the expense of
their PM
• have to add phospholipids and proteins OR change
a. Fluid-phase
the membrane itself – membrane assembly
• Formation of invaginations which will
become larger until the two sides of
o RECEPTOR-MEDIATED ENDOCYTOSIS
the membrane fuse, sealing the neck of
▪ Specific uptake
the PM at the original site of
▪ High affinity receptors permit selective
invagination forming a fluid-filled
concentration of ligands from medium
vesicles
▪ Pits (invaginations) is coated with filamentous
b. Absorptive
material called clathrin
• Formation of invaginations bringing the
▪ Protein association:
receptor inside it for digestion (called
• Clathrin – coating; allows selective uptake
internalization)
• Adaptin – allows vesicle formation
• Some receptors are digested like that
• Dynamin – GTP-hydrolyzing; for pinching off pit
of insulin receptor (that is why people
▪ Low density lipoprotein – receptor binding
consuming too much sweets develop
▪ Disorder in LDL -familial hypercholesterolemia
Type II diabetes); some are returned
▪ Viral transfection mechanism
back to the membrane like that of LDL
receptor
Additional information about Clathrin

• has three-limbed structure (triskelion)

• each limb made of one light and one heavy chain of
clathrin
• polymerization of clathrin into a vesicle
o directed by assembly particles composed of
four adapter proteins that interact to the
receptors ensuring the selectivity of uptake
o involves PIP2 (phosphatidylinositol 4.5- o PHAGOCYTOSIS
biphosphate) for vesicle assembly ▪ also called “cell eating”
▪ involves ingestion of large particles: whole cells
(bacteria), particles (viruses) and cellular debris

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 ▪ involves specialized cells
➢ macrophages – for more and prolong infection;
can engulf an entire cell
➢ neutrophils – present in CBC; for acute
inflammation
▪ during severe infections, macrophages ingest a
large volume of their cell membrane through this
process
▪ can ingest their while CM in 30mins
▪ ingest 25% of their volume per hour
• internalize 3% of its PM each minute
o leads to membrane assembly
• mechanism like that of absorptive pinocytosis –
involves formation of pits and primary and
secondary phagolysosomes
• requires activation of cell surface receptors
• requires pseudopod formation from actin filament
remodeling
• ingested particles are directed to primary lysosome
that will hydrolyze the particles
EXOCYSTOSIS
• Release of macromolecules to the exterior (products
coming from the cell going to the outside)
• Involved in membrane remodeling
• From the site of production (ribosomes) that is
attached to the ER – transported to Golgi apparatus
for processing, packaging, and formation of vesicles
o When there’s signal, vesicles will fuse with the
PM and extrude its contents outside
• Signal for initiation is often via a hormone binding to
cell surface receptors – increasing Ca2+
o Ca2+ triggers exocytosis
Three fates of molecules released thru exocytosis
1. Attach to cell surface to become peripheral proteins
( eg antigen)
2. May become a part of extracellular matrix (collagen,
GAGs/glycosaminoglycans)
3. May enter ECF and signal other cells (hormones and
enzymes)
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*exocytosis involves the contact of two inside surface
(cytoplasmic side) monolayers, whereas endocytosis
results from the contact of two outer surface monolayers
MEMBRANE, LIPID, AND PROTEIN ASSEMBLY
MEMBRANE ASSEMBLY
• Both lipids and proteins are inserted independently
in membranes
• Lipids and proteins turnover independently and at
different rates
• Topogenic sequences (signal N terminal or internal
or stop) are important in determining the structure
of proteins in membranes
• Final sorting of many membrane proteins occur in
the trans golgi
• Specific sorting sequences guide proteins to
particular organelles
o Eg mannose-6-PO4 guides hydrolases
destined for lysosomes while KDEL [Lys-
Asp-Glu-Leu] specify proteins for the ER)
LIPID ASSEMBLY
• Enzymes responsible reside in the cisternae of ER
• Phospholipids self-assemble as they are synthesized
into the thermodynamically stable bilayers
• Lipid vesicles migrate and fuse with golgi apparatus
PROTEIN ASSEMBLY
membrane which in turn fuse with plasma
membrane
• Explained by the signal hypothesis
o The signal hypothesis proposes that proteins
destined for secretion, which involves the
movement of the protein across a biological
membrane, are originally manufactured with an
initial sequence of amino acids that may or may
not present in the mature protein
• Requires ER – golgi apparatus – vesicles – plasma
membrane
• The information for both modes of translocation is
encoded in the protein in the form of a short-lived
sequence extension (signal sequence)
• Additional information resides in the ribosome in
the case of co-translational translocation, which
proceeds via a ribosome – membrane junction
• Translocation is mediated by specific receptors
(ribosome and/or signal receptors) which are
 restricted in their location to distinct cellular
membranes

2 kinds of proteins:

• Those synthesized by membrane bound ribosomes

(secreted proteins and integral proteins) that
contain a signal peptide at their N-terminal
• Those synthesized by free ribosomes (cytosolic
proteins, extrinsic proteins in the inner plasma
membrane leaflet) that lack signal peptide

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