Physiology

Cell Physiology
1

Semester
Caterine Memoracion, MD | 16 08 2017
o Little structural function as part of glycoproteins
OUTLINE (2-level)  Ions
I. Cell o Provides inorganic chemicals for cellular reaction
A. Composition o Most important ions:
B. Major Parts or Compartments  Na+, K+, Cl-, Ca2+, Mg+, PO4-, SO4-, HCO3
C. Structures and Its Functions
D. Movements of the Cell B. MAJOR PARTS OR COMPARTMENTS
II. Cell Membrane
A. Functions of Cell Membrane
B. Composition and Its Functions
C. Membrane Junctions
i. Types
ii. Components
III. Membrane Transport
A. Through The Membrane
B. Across The Membrane
C. Epithelial Transport
IV. Apoptosis
V. Cellular Communication
VI. Cell Signalling
VII. Membrane Receptors
VIII. Homeostasis
IX. Body Fluid Compartments
X. Ionic Composition of Cells

I. CELL
 All cells share common elements and functions Fig 1. The Cell and Its Parts.
 Cells are organized into 3 main regions:
o Nucleus  Nucleus
o Cytoplasm o Control center of the cell
o Plasma membrane o Contains large quantities of DNA – genes
(Chromatin -> DNA -> genes)
A. COMPOSITION o Control and promote reproduction of cell
 Water  Nuclear Membrane
o 70-85% o An envelope that surrounds nucleus
o Principal fluid medium of the cell o Double membrane with spaces between called
o Where chemical reactions take place perinuclear cisterns.
 Proteins o Contains nuclear pores through which transport
o 10-20% of protein and mRNA occurs
o Functional Proteins (globular/enzymatic) – Act as  Nucleolus
enzymes to control metabolic functions o Staining structure inside nucleus
o Structural Proteins (fibrous) – Form the o A patchwork of granules rich in RNA
cytoskeleton of the cellular organelles o Site of ribosome synthesis
o Serve as cell adhesion molecules, carriers, pumps, o Most prominent and numerous in growing cells
Ion channels, enzymes, and structural function  Chromatin
 Lipids o Basophilic material composed of DNA and
o 2% of cell mass associated proteins (histones)
o Form the cell membrane and intracellular o Scattered throughout the nucleoplasm
membrane barriers that separate the cell o Condenses to form chromosomes when cell
components divides
o Fats stored in cells are the main storehouse of  Cytoplasm
energy giving nutrients o Aqueous solution that contains organic
 Carbohydrates molecules, organelles and inclusions
o 1% of cell mass  Plasma Membrane
o Major role in nutrition of the cell / major and o Separates intracellular contents from
immediate source of energy extracellular environment

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o A lipid bilayer with associated proteins o Site of protein synthesis

C. STRUCTURES AND ITS FUNCTIONS D. MOVEMENTS OF THE CELL

 Mitochondria
o Powerhouse of the cell
o Site of ATP synthesis or energy production. ATP is
generated through oxidative phosphorylation
o Ca2+ storage
o Bounded by a two-lipid bilayer membrane
o Contains DNA controlling replication
 Endoplasmic reticulum
o Highway of the cell
o A network of tubular and flat vesicular structures
in the cytoplasm
o Connected to the nuclear membrane
 Rough Endoplasmic Reticulum
o Ribosomes are attached to the cytoplasmic side
of the membrane
o Site or protein synthesis
o Site of the translation of mRNA sand
posttranslational modification of proteins to be
secreted out of the cell.
 Smooth Endoplasmic Reticulum
o No attached ribosomes
o Site of lipid synthesis
o Site of steroid synthesis
o Site of detoxification process in other cells
o Ca2+ storage
 Golgi apparatus
o Stack of flattened membrane sac
o Sorts the proteins from the Rough ER and packages
them to for delivery to other parts of cells.
o Packaging of the cell
 Lysosomes
o Vesicular organelles formed from Golgi apparatus
o Contains hydrolytic enzymes
o Digestive system of the cell
 Peroxisome (Microbodies)
o Bud off from the ER
o Contains oxidative enzyme
 Cytoskeleton
o Microfilament (actin filaments)
 A contractile element in muscle cells
o Intermediate filament
 For structural support
o Microtubules
 Intracellular transport of vesicles driven
by motor proteins
 Kinesin - centre to periphery
 Dynein - periphery to centre
 Chromosome movement during mitosis
and meiosis
 Movement of cilia and flagella
 Ribosome
o Complex structure containing mixture of protein
and RNA or Ribonucleoprotein (RNP)
o Impart the rough appearance of the organelle
o Attached to the surface of Rough ER
 Ciliary movement
o Responsible for whip-like movement
 Flagella
o Responsible for the movement of sperm
 Amoeboid movement
o Movement of the entire cell in relation to the
surroundings
o E.g. Movement of WBC through tissues
II. CELL MEMBRANE
 Also called plasma membrane
 In eukaryotic cells, it has a 5nm thick lipid bilayer with
associated proteins.
 Fluid mosaic model
Fig 2. A Schematic Diagram of the Cell Plasma Membrane.
A. FUNCTIONS OF CELL MEMBRANE
 Selective permeability – regulates transport of molecules
into and out of the cell
 Semipermeable – act as a gatekeeper where it restricts
passages of same substances while permitting the passage
of others
 Permeability barrier – maintains differences in ionic
composition and establishes ionic gradients between the
extra and intracellular compartments. (Major Cation –
Sodium, Major Anion – Chloride)
 Determination of cell shape linking the cytoskeleton to the
plasma membrane
 Cell communication through neurotransmitters and
hormone receptors and signal transduction pathways
 Tissue organization through cell junctions
 Enzymatic activity
 Amphipathic – have both hydrophilic (phosphate head) and
hydrophobic (fatty acid tails) parts.
B. COMPOSITION AND ITS FUNCTIONS
 Membrane composition
o Protein 55%
o Phospholipids 25%
o Cholesterol 13%
o Other lipids 4%

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o Carbohydrates 3% o Glycerol

Table 1. Plasma Membrane Components and Functions. Table 2. List of Common Phospholipids.

1.2 Cholesterol
 Functions as a “fluidity buffer”, tend to keep the
membrane fluidity in an intermediate range
 Stabilize the membrane at normal body temeprature
(37C)

1. Membrane Lipids 1.3 Glycolipids

 Lipid bilayer with fluid like properties
 Less abundant
 Primarily responsible for the passive permeability
 Functions as a receptor
properties of the plasma membrane
 Conatains a 2 fatty acyl chains linked to polar head groups
 Made up of:
that consists of carbohydrates.
o Phospholipids (major lipid)
o Cholesterol
The fluidity of the membrane is determined by temperature and
o Glycolipids
lipid composition.
 ↑ temperature = ↑ membrane fluidity
 Present unsaturated fatty acyl chains in phospholipids and
glycolipids = ↑ membrane fluidity

2. Membrane Proteins

Fig 3. Types of Lipids in the Cell Membrane.

1.1 Phospholipids Fig 4. Diagram of Membrane Proteins

 Are amphipathis molecules that contain a charges (polar)
hydrophilic head and two (non polar) hydrophobic fatty 2.1 Integral or Intrinsic Membrane Proteins
acyl chains.  Embedded in the bilayer
 Majority has a glycerol backbone where the fatty acyl  Also called transmembrane proteins
chains and alcohol are attached  Act as channel or carrier proteins
 The most common alcohols linked to glycerol via a  May pass through the membrane multiple times
phosphate group are:  Hard to isolate from the membrane, requires the use of
o Choline detergents
o Ethanolamine  Have both the hydrophobic and hydrophilic regions
o Serine o Ion channels
o Inositol o Transport proteins

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o Receptors o Leak channels
o Guanosine 5’- triphosphate- binding proteins (G  Gated Channels
proteins) o Chemically-gated channels
 Controlled by messenger molecule or
2.2 Peripheral or Extrinsic Membrane Proteins ligand
 Loosely attached to the surface by electrostatic o Voltage-gated channels
interactions.  Controlled by the electrical state of the
 Act as enzymes or signal transmitter cell
 Not embedded in the cell membrane o Mechanically-gated channels
 Not covalently bound to membrane components  Controlled by the physical state of the
 Can easily be removed from the membrane cell
 Solute Carriers – bind molecules and cause conformational
C. MEMBRANE JUNCTIONS changes
 Needed for cell to cell communication o Uniporter
o Symporter
o Antiporter
 ATP-dependent transporter
o Uses energy from ATP to move ions across the
membrane

A. TRANSPORT THROUGH THE MEMBRANE

According to the need for energy:
 Passive Transport
o Simple Diffusion
o Facilitated Diffusion
 Carrier mediated
 Channel Mediated
o Osmosis
o Filtration
 Active Transport
o Primary Active Transport
Fig 5. Location of Membrane Junctions. o Secondary Active Transport
 Co-transport or Symport
1. Types  Countertransport or Antiport
a. Tight Junctions – Impermeable junctions that prevents
molecules from passing through intercellular space. 1. Passive Transport
b. Desmosomes – Anchoring Junctions that bind adjacent cells  Transport substances along an electrochemical gradient
together (concentration, pressure or electrical gradient)
c. Gap Junctions – Communicating Junctions that allows ions  Downhill movement
and small molecules to pass for intercellular  (-) carrier except facilitated diffusion
communication  (-) energy
 Stops once equilibrium is reached
2. Components
 Intracellular anchor proteins 1.1 Simple Diffusion
 Transmembrane adhesion or linker proteins (TLP)  Spontaneous process by which molecules move from a high
o Integrins (cell-matrix) or cadherins (cell-cell) to low concentration due to inherent kinetic energy
 Cytoskeletal elements (random motion)
 Rate Of Diffusion Faster:
III. MEMBRANE TRANSPORT o Smaller Molecules
 Membrane transport proteins o At Elevated Temperature
o Water channels (Aquaporins) o In Large Concentration Gradient
 Main route for movement of water into o Low Viscosity Medium
and out of cells o Lipid Solubility
o Ion channels
 Open channels
 Gated channels
 Open Channels
o Pores

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Fig 6. Diffusion. Note: the molecules move from a high (left) to low
(right) concentration.
Diffusion of Water Soluble Substances
 Water and very small, uncharged water-soluble molecules
and ions can pass through the membrane much more
rapidly than would be predicted by their lipid solubility
o Uncharged molecules can pass between adjacent
phospholipid molecules without dissolving in the
bilayer
o Protein channels (water molecules and ions)
Fig 7. Diffusion of Water Soluble Substances.
 The rate at which a molecule diffuses from point A to point
B can be quantified by Fick’s first law of diffusion:
∆𝐶
J = −DA
∆𝑋
Where,
J = flux or rate of diffusion per unit time
D = diffusion coefficient
A = area across which the diffusion is occurring
∆C – concentration gradient
∆X = distance along which the diffusion is occurring
1.2 Facilitated Diffusion
 Transport of substances down their concentration or
electrochemical gradient using carrier proteins
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 Does not require energy
 Conformational change occurs randomly
 Example: Glucose transporter
Fig 8. Facilitated Diffusion. Note: This figure shows a glucose
transporter.
1.3 Osmosis
 Net diffusion of water
 Passive movement of water across a semi-permeable
membrane down its concentration gradient (net diffusion
of water across a membrane)
 Movement: From low to high concentration
 Occurs through aquaporins
 Requires
o Concentration gradient for a solute across the
membrane
o Relative impermeability of the membrane to the
solute
Fig 9. Osmosis. Note: This figure shows the movement of water with
relation to the compartment’s solute concentration. Since the left
compartment contains more solutes compared to the other, the water
shifts to the left.
Osmotic Pressure
 Amount of pressure required to stop movement of pure
water into the solution
 Dependent on the number of dissolved particles, not the
mass of particles in the solution
 Must take into account the ionization of the solute
Osmolarity
 Osmotic pressure generated by dissolved solute molecules
in 1L of solvent
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 Dependent on temperature  Pressure generated by large molecules (proteins) in a
solution
Osmolality  Responsible for the movement of fluid between ECF and ICF
 Osmotic Pressure generated by these solute molecules
dissolved in 1kg of solvent 2. Active Transport
 Independent of temperature  Transport substance against an electrochemical gradient
 Isosmotic – same osmolality o Concentration
o Pressure
Tonicity o Electrical
 Related to the effect of the solution on the volume of the  Uphill movement
cell  (+) carrier
 Types  (+) energy
o Isotonic – do not change of volume of the cell  Exhibits saturation kinetics, specificity and competitive
o Hypotonic – causes the cell to swell inhibition
o Hypertonic – causes the cell to shrink
2.1 Primary Active Transport
 Transport one or more substances
 Directly linked to cellular metabolism (coupled with the
hydrolysis of ATP)
 Transport substance against an electrochemical gradient
 Examples
o Na+, K+ ATPase
o Ca++ ATPase
o H+, K+ ATPase
Fig 10. Tonicity. Note: This figure shows the effects of tonicity on red
blood cells, showing the solute concentrations in and out the cell, and
2.2 Secondary Active Transport
its relation to the flow of the water.
 Transport two or more substances
Effective Osmole  Linked to energy indirectly
 Does not cross the membrane  Uses the ion concentration gradient established by primary
 Exerts osmotic pressure active transport to drive (uphill movement) transport of
substances
Ineffective osmole o Strong inward gradient for Na+ due to Na-K
 Crosses the membrane ATPase pump which acts as a storehouse of
energy
 Does not exert osmotic pressure

1.4 Filtration
 Substances and solvent move across the membrane driven
by a hydrostatic pressure gradient
 Solute-containing fluid is pushed from a high pressure area
to a lower pressure area

Fig 12. Primary Active and Secondary Active Transport.

Co-transport or Symporter
 Two or more molecules are transported in the same
direction
 Example: 1Na+, 1K+, 2Cl- symporter
Fig 11. Filtration. Note: Hydrostatic pressure refers to the pressure
exerted by the heart, and the effect of the gravity in the blood vessel. Countertransport
 Two or more molecules transported in opposite directions
Oncotic Pressure  Example: Na+-H+ antiporter

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 It is the uptake of large substance from the cell and this is
engulfed by the cell membrane and coated with the
vesicle.
 The plasma membrane extends and captures large
molecules.
 The integrity of the membrane is not lost during the
process
 An important characteristic of cells in the immune system
(e.g., neutrophils and macrophages).
o Not all WBCs are phagocytic (LYMPHOCYTE)
 Often but not always, Phagocytosis is a receptor mediated
process.

Fig 13. Co-transport and Countertransport.

B. TRANSPORT ACROSS THE MEMBRANE

VESICULAR TRANSPORT
 Also called as bulk transport
 Does not require carriers Fig 14. Phagocytosis (cell-eating)
 Vesicles are created by the cell that allows transfer of the
contents between cellular compartments.
1.2 Pinocytosis
 Involves activity of the whole cell membrane
 Cell drinking; for liquids
o Initial formation of Vesicle  The vesicle created
 Nonspecific uptake of small molecules and water into the
will eventually become a vacuole  Movement of
vacuole  surrounded by Lysosomes  Enzymes cell.
from Lysosomes will digest everything in the cell  Prominent feature of the endothelial cells that line
(INWARD TRANSPORT) capillaries
 Solute and water can be brought into the cell by the process  Responsible for a portion of the fluid exchange that occurs
of endocytosis and released from the cell by the process of across blood vessels.
exocytosis.  Uptake of ECF and soluble material
 Occurs when plasma membrane folds inward to form a
1. Endocytosis channel allowing substances to enter the cell and encircled
 The substances that are outside the cell are engulfed by within a pinocytic vesicle.
the plasma membrane and become enclosed with the
vesicle.
 Allows the cell to absorb or take in substances.
 Allows material to enter the cell without passing through
the cell membrane (NO PASSAGE through membrane)
 Subdivided into 3 mechanisms: Phagocytosis, Pinocytosis,
Receptor-mediated endocytosis
 Involves a “docking” process wherein there is binding with
a specific membrane protein (receptor) forming a vesicle
in the membrane called CLATHRIN, that allows cell to
absorb or take in substances and helps in creating vesicles. Fig 15. Pinocytosis (cell drinking)
 Clathrin, Adaptin, Thymine  present in membrane
1.3 Receptor-Mediated Endocytosis
 Accessory protein: Adaptin & Dynamin
 Allows the uptake of specific molecules into the cell.
 Molecules bind to specific receptors on the surface of the
1.1 Phagocytosis
cell and then coated with the vesicle.
 Cell-eating; for solids
 Involves a number of accessory proteins including adaptin,
 Ingestion of large particles, such as bacteria, whole cells,
tyramine, clathrin, and the GTPase dynamin.
or portions of degenerating tissue.

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o A receptor on the surface of the cell binds the
ligand. A clathrin-coated pit is formed, with
adaptin linking the receptor molecules to the
clathrin. Dynamin, a GTPase, assists in separation
of the endocytic vesicle from the membrane.
Once inside the cell, the clathrin and adaptin
molecules dissociate and are recycled. The
uncoated vesicle is then ready to fuse with other
organelles in the cell (e.g. Lysosome).
Fig 16. Receptor-Mediated Endocytosis
2. Exocytosis
 It is the process of releasing the substance from the cell.
 Substances (e.g. hormones, mucous, cell wastes) are
packaged, enclosed in a vesicle and then brought to the
plasma membrane where they are secreted.
 Vesicles migrate and combine with plasma membrane.
 Material is emptied to the outside.
 Explains the ability of the cells to secrete or excrete
substances.
 Starts at the cytoplasm and move the vacuole towards the
membrane.
o Golgi apparatus is responsible for exporting
agents
o Microtubules use protein  Kinesin
 Can be either constitutive or regulated.
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Fig 17. Constitutive and Regulated Transport
2.1 Constitutive Pathway
 Almost no control
 Continuous, partially-regulated pathway
o e.g. Mucous secretion
o e.g. Plasma cells that are secreting
immunoglobulin; fibroblasts secreting collagen
2.2 Non-constitutive Pathway
 Fully regulated pathway using a ligand that will initiate the
transport.
 Specific
 Directed by hormones or neurosignals
 Occurs in endocrine cells, neurons, and exocrine glandular
cells (pancreatic acinar cells).
o In these cells the secretory product (e.g.
hormone, neurotransmitter, or digestive
enzyme), after synthesis and processing in the
RER and Golgi apparatus, is stored in secretory
granules until an appropriate signal (may be
hormonal or neural) for secretion is received.
2.3 Transcytosis/Cytopempsis
 Transport of substance rapidly through a cell.
 Activity is observed when endocytosis across one
membrane of the cell is directly followed by exocytosis
across the opposite membrane.
 Only possible if the endocytosis and exocytosis do not occur
of the same area; the two activities happen in different
parts of the cell.
 Agent should travel the whole cell.
 Common in the intestines and renal tubular cells
C. EPITHELIAL TRANSPORT
 Movement of substances across an epithelial surface
 The transport of substances from one membrane to
another
 Involves 2 pathways:
o PARACELLULAR
 Substances are transported between
adjacent cells across a tight junction.
 Occurs primarily in small ions and water
molecules
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 Passive in nature o Neurons transmit electrical signals along their
 Limited by tight junctions and small axons and release neurotransmitters at synapses
area for diffusion that affect the function of other neurons or cells.
o TRANSCELLULAR  Endocrine
 THROUGH THE CELL o Hormones are released by endocrine cells reach
 It involves the movement of a their target cell via bloodstream.
substance through the cell, from one  Autocrine
side of the cell to another side of the o Release of a molecule that affect the same cell or
cell. other cell of the same type.
 There is movement into the cell both by
diffusion (passive) and mediated VII. MEMBRANE RECEPTORS
transport (active)
 Ion channel linked receptor or ligand gated ion channel
 Na-K ATPase located in the basolateral membrane
o Mediates synaptic signalling
 G protein coupled receptor
o Mediated by G proteins
 Catalytic receptor
o Enzymes that causes kinases to phosphorylate
proteins hence alters protein activity
 Nuclear receptors
o Binds to DNA to regulate gene expression

VIII. HOMEOSTASIS

Fig 18. Paracellular and Transcellular Transport  Homeostasis

o [Gk] homeo, meaning "same"
IV. APOPTOSIS o [L] stasis, meaning standing
o Maintaining steady-state
 Programmed death of death cells  To maintain homeostasis
 Overall compaction of a cell and its nucleus and the orderly o Set point
dissection of the chromatic by endonucleases o Mechanisms monitoring deviations from a set
 Rate of Destruction = Rate of Replacement point
 Mediated by proteolytic enzymes called: Caspases  Parts
 RBC is NOT included (anucleated) o Receptor
 Two phases of Apoptosis o Control center
o Activation phase o Effector
 Self-Destruction  When excess water is added = ↓ ECF osmolality; when
 Use enzyme as Caspase excess water is lost = ↑ osmolality
o Execution phase  Normal cellular function requires composition of ICF be
 "Eat me" markers for phagocytes tightly controlled and volume cells must be maintained
 Splenic Macrophages kills RBC
 Monocytes =source of phagocytic cells Control Mechanism
 Evolve around a feedback system
V. CELL COMMUNICATION o Negative feedback system
 Gap Junction  Effects are negative with respect to the
o Communication junctions between adjacent cells initiating stimulus
o Signals pass directly from cell to cell without  Allows maintenance of homeostasis
reaching ECF since it keeps the condition constant
 How most control systems of the body
VI. CELL SIGNALLING act

 Juxtacellular
o Signalling molecules remain part of a cells surface
and bind surface receptors of the target cell when
the two cells make direct physical contact.
 Paracrine
o Released by one type of cell and act on another
type of cell
o Reach the target cell by diffusion
 Synaptic

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o More complex type of control system
o Adaptive control
o A delayed type of negative feedback
o Has a sensor that can anticipate environmental
changes and prompt the system to act before
alterations begin to affect it

IX. BODY FLUID COMPARTMENTS

Fig 19. Negative Feedback Control. Note: This figure shows the
relationship of the receptors in the blood vessels and blood pressure.

o Positive feedback system

 Intensify the initial stimulus leading to
enhancement of the response
 Better known as vicious cycle
 May have destabilizing effect and can
be harmful
Fig 21. Relationship between Volumes of Various Body Fluid
Compartments.

 Total body water = 60%, therefore TBW = 0.6 x body weight

 Total body weight attributed to water varies according to
adipose tissue (< less) and age (< younger)
 Total body water is distributed between two compartments
divided by the cell membrane: extracellular fluid (ECF) and
intracellular fluid
 Intracellular fluid – 2/3 of body water, therefore ICF = 0.4 x
body weight
 Extracellular fluid – 1/3 of body water, therefore ECF = 0.2
x body weight
 ECF is subdivided into interstitial fluid and plasma by
capillary wall
 Interstitial fluid – 3/4 of ECF
 Plasma – 1/4 of ECF
 Third space – due to pathological reasons
 Compartmentalization between the interstitial and
intravascular compartments is governed by STARLING’S
FORCES
o "… There must be a balance between the
hydrostatic pressure of the blood in the capillaries
and the osmotic attraction of the blood for the
surrounding fluids."
o "… And whereas capillary pressure determines
transudation, the osmotic pressure of the
proteins of the serum determines absorption. “
Fig 20. Positive Feedback Loop. Note: This figure shows the release of
oxytocin to cause uterine contraction. X. IONIC COMPONENT OF CELLS

 Feed Forward System  ICF is characterized by low [Na+] and high [K+]

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 ECF is characterized by high [Na+] and low [K+]
 Na+, K+ - ATPase – transports 3 Na+ ions out of the cell and
2 K+ ions into the cell
 Leakage of K+ out of the cell through K+-selective channels
that is a major determinant of membrane voltage
 Glucose and amino acids are taken up by the cell via
secondary active cellular uptake
 Extrusion of H+ from the cell contribute to the maintenance
of intracellular pH

REFERENCES
1. Boron WF, Boulpaep EL. Medical Physiology. 2nd ed,
updated. New York: Saunders-Elsevier, 2012.
2. Hall JE. Guyton and Hall Textbook of Medical Physiology.
13th ed. New York: Saunders-Elsevier, 2016.
3. Koeppen BM, Stanton BA (eds). Berne and Levy Physiology.
6th updated ed. Philadelphia: Mosby-Elsevier, 2010.
4. Lecturer’s PPT

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