Chap 11

Cell–Cell Interactions

Ki-Young Kim
[email protected]
국경대 324호

Roadmap 11
In this chapter you will learn how
Cells modify their environment and interact
with one another via social networks
by exploring
The cell surface 11.1
then asking
How do adjacent cells How do distant cells
connect and communicate? connect and communicate?
11.2 finally
looking closer at exploring
Cell-cell Signaling in Signaling between
attachments multicellular unicellular
and gaps organisms 11.3 organisms 11.4

Review of Plasma Membrane Structure

and Function
• The plasma membrane is made up of a phospholipid bilayer with
many interspersed proteins
- Proteins may be integral or peripheral

• The primary function of the plasma membrane is

- To create an environment inside the cell
- Different from conditions outside

• The selective permeability of the membrane controls the flow of

materials into and out of the cell
 The Structure and Function of an
Extracellular Layer
Structure
• Most cells possess a protective layer or wall that forms just beyond
the membrane
• This layer generally consists of a fiber composite
- A cross-linked network of long filaments
- Surrounded by a stiff ground substance
Function
• The rods or filaments protect against tension
• The ground substance protects against compression

Figure 11.1 Fiber Composites Resist Tension and Compression.

Concrete (the “ground

substance”) resists Steel rods
compression (the “fibers”)
resist tension

The Primary Plant Cell Wall

• When new plant cells form, they secrete a fiber composite called a
primary cell wall
• Wall is composed of
- Long strands of cellulose
- Bundled into microfibrils
- That form a crisscrossed network
 The Primary Plant Cell Wall
• Wall is filled with hydrophilic gelatinous polysaccharides
- Such as pectin
- Keep the cell wall moist

• The primary cell wall

- Defines the shape of the plant cell
- Counteracts the turgor pressure it experiences

Figure 11.2 Primary Cell Walls of Plants Are Fiber Composites.

Side view Top view

Cellulose
microfibrils
Primary Cross-links
cell wall
Pectin

Plasma
membrane

1 m
50 nm

The Secondary Plant Cell Wall

• Some cells secrete a secondary cell wall
- It is inside the primary cell wall

• Secondary cell wall structure correlates with the specific cell’s

function
• In cells that form wood, the secondary cell wall contains lignin
 Central Plasma
vacuole membrane
Cell Walls of Plants of cell Secondary
cell wall
Primary
cell wall
Central
Middle
vacuole
lamella
of cell

1 µm
Central vacuole
Cytosol
Plasma membrane

Plant cell walls

Plasmodesmata

The Extracellular Matrix in Animals

• Most animal cells secrete a fiber composite called the extracellular
matrix (ECM)
• One of the ECM’s most important functions is structural support
• The amount and composition of the ECM vary depending upon the
cell type

Extracellular Matrix Structure and

Function
• The ECM consists of
- A ground substance formed of gelatinous polysaccharide
- A network of protein fibers

• The most common ECM protein fiber is collagen

- Collagen is more elastic than cellulose
- It forms a flexible extracellular layer
 Extracellular Matrix Structure and
Function
• The ECM also helps cells
- Stick together
- Form protein–protein attachments
- Link the ECM directly to the cell’s cytoskeleton

Extracellular matrix (ECM) of an animal

cell.
Collagen Polysaccharide
EXTRACELLULAR FLUID molecule
Proteoglycan Carbo-
complex hydrates
Fibronectin Core
protein

Integrins

Proteoglycan
molecule
Plasma
membrane Proteoglycan complex

Micro- CYTOPLASM
filaments

(a) Collagen proteins consist of three polypeptide chains

that wind around one another.
3 chains
Figure 11.3 The Extracellular
1.5-nm
Matrix Is a Fiber Composite. collagen
protein

(b) Proteoglycan complexes form the ground substance of

the animal ECM.

Proteoglycan

Polysaccharides Core protein

Proteoglycan
complex

Proteoglycan

0.5 m
 The ECM and Cytoskeleton Are Directly
Linked
• The ECM is strengthened by connections to transmembrane proteins
• Actin protein filaments in the cytoskeleton bind to transmembrane
integrin proteins
• Integrins bind to ECM proteins such as fibronectins, which then bind
to collagen
• Direct linkage between the cytoskeleton and ECM
- Keeps individual cells in place
- Helps adjacent cells adhere to each other
- Breakdown can lead to metastasis of cancerous cells

Figure 11.4 Integrins Connect the Extracellular Matrix to the Cytoskeleton.

Plasma
membrane Extracellular matrix
Cytoskeleton (ECM)

50 nm

Actin Integrin Laminin Proteoglycans Collagen Collagen

filaments (structural fibril) (anchoring fibrils)

How Do Adjacent Cells Connect and

Communicate?
• Unicellular organisms do not connect to one another
• The basis of multicellularity is physical connections between cells
• Cells of multicellular organisms
- Adhere to one another
- Have specific, distinct structures and functions

• Tissues are comprised of

- Groups of similar cells
- Performing similar functions
 Connections between Plant Cells
• The extracellular space between adjacent plant cells comprises three
layers:
1. Primary cell wall of one plant cell
2. Middle lamella
3. Primary cell wall of another plant cell

• Plant cells are glued together by the middle lamella

- Continuous with adjacent plant cells’ primary cell walls
- Comprised of gelatinous pectins

Figure 11.5 The Middle Lamella Connects Adjacent Plant Cells.

Primary cell wall

Secondary cell wall
1 m Plasma membrane

Cell–Cell Attachments
• The structures that hold cells together vary among multicellular
organisms
 Figure 11.6 An Array of
Structures Are Involved
in Cell–Cell Adhesion
and Communication
between Animal Cells.

Tight junctions
seal cells together.

Desmosomes
connect the
cytoskeletons
of cells.

Gap junctions
act as channels
between cells.
Space between cells

Connections between Animal Cells

• A middle-lamella-like layer
- Made of gelatinous polysaccharides
- Exists between cells in many animal tissues

• The polysaccharide glue may be reinforced by cable- like proteins that

span the ECM to connect adjacent cells

Connections between Animal Cells

• Epithelial tissue is composed of sheets of cells
- Cover organs
- Line body cavities

• Many types of structures connect neighboring epithelial cells,

including
- Tight junctions
- Desmosomes
 Tight Junctions
• Tight junctions
- Are composed of specialized proteins
- In the plasma membranes of adjacent animal cells

• These proteins line up and bind to each other

- Stitching the two cells together to form a watertight seal
- Between the two plasma membranes

Tight Junctions
• Tight junctions
- Are usually found between cells in tissues that form a barrier
- Such as the tissue lining the stomach or bladder

• Tight junctions are dynamic and variable

Figure 11.7 In Animals, Tight Junctions Form a Seal between Adjacent Cells.

(a) Electron micrograph of a tight junction in longitudinal (b) Three-dimensional view of a tight junction
section

A tight junction forms a

watertight seal between
epithelial cells
Plasma membranes
of adjacent cells
Tight
junction
Membrane proteins
bind to one another to
form a tight junction.

0.1 m
 Desmosomes
• Desmosomes are made of proteins that link the cytoskeletons of
adjacent cells
• Desmosomes are common in epithelial and muscle tissue
• These proteins bind
- To each other
- To the proteins that anchor cytoskeletal intermediate filaments

Figure 11.8 Adjacent Animal Cells Are Linked by Desmosomes,

Which Bind Cytoskeletons Together.

(a) Micrograph of desmosome in longitudinal section (b) Three-dimensional view of desmosome

Plasma membranes
of adjacent cells

Anchoring
proteins
inside cell
Desmosome
Membrane
proteins that
link cells

Intermediate
filaments

0.1 m

Selective Adhesion
• Selective adhesion in sponges
- Dissociated cells could aggregate and adhere to cells of the same tissue type
- They eventually reform as functional adult sponges
Figure 11.9 Evidence for Adhesion Proteins on Animal Cells.
Do animal cells have adhesion proteins on their surrfaces?
Selective adhesion is due to specific membrane proteins.
Selective adhesion is not due to specific membrane proteins.

Membrane
proteins

1. Isolate membrane
proteins.

2. Produce antibodies.
Antibodies

Experiment 1: Experiment 2:
3. Treat cells with
antibodies and observe.

Experiment 2:
Experiment 1: Cells do not adhere.
Cells adhere
normally.

The protein that was blocked in experiment 2 (called a cadherin) is involved in cell–cell adhesion.

The Molecular Basis of Selective Adhesion

• Animal cells attach to each other selectively because
- There are several classes of cell adhesion proteins
- Each major cell type has its own cell adhesion proteins

• These cell–cell connections are also species and tissue specific

• Cadherins are the adhesion proteins in desmosomes

Cell Communication via Cell–Cell Gaps

• Direct connections between cells in the same tissue
- Allow cells to communicate
- Work together in a coordinated fashion

• Plant cells are connected by plasmodesmata

- Gaps in the cell wall
- Where the plasma membranes, cytoplasm and smooth ER of two cells connect
 Cell Communication via Cell–Cell Gaps
• In animal tissues, gap junctions
- Connect adjacent cells by forming channels
- Channels allow the flow of small molecules between cells

Figure 11.10 Adjacent Animal Cells and Adjacent Plant Cells Communicate Directly.
(a) Gap junctions create gaps that connect animal cells.

Gap
junctions Membrane proteins
from adjacent cells
line up to form
a channel.

20 m

(b) Plasmodesmata create gaps that connect plant cells.

Plasmodesma Smooth
with a tubule of endoplasmic
endoplasmic reticulum reticulum
passing through Cell wall Cell wall
Cell walls of cell 1 of cell 2
Membrane Membrane
0.1 m
of cell 1 of cell 2

Summary of Eukaryotic Cell–Cell

Attachments
• Bind adjacent cells to each other:
- Middle lamella
- Continuous ECM
- Tight junctions
- Desmosomes
- Cadherins

• Allow adjacent cells to communicate:

- Plasmodesmata in plants
- Gap junctions in animals
 How Do Distant Cells Communicate?
• The activities of cells, tissues, and organs
- Occur in different parts of a multicellular organism
- Are coordinated by long-distance signals

• Small molecules may be transported through plant tissues within

- Symplast = shared cytoplasm
- Apoplast = extracellular space

Figure 11.11 Most Plant Tissues Are Divided into Two Compartments
—Symplast and Apoplast.

Cell membrane
Plasmodesmata
interconnect cells Cell wall
to form a continuous Cytoplasm
membrane system: Lamella
the symplast Vacuole

Symplast

Apoplast

Hormones Are Long-Distance Messengers

• A hormone is
- An information-carrying molecule
- Secreted from a cell
- Circulates in the body
- Acts on target cells far from the signaling cell
 Hormones Are Long-Distance Messengers
• Hormones are usually
- Small molecules
- Typically present in minute concentrations
- Have a large impact on the condition of the organism as a whole

• Function and chemical structure of hormones vary widely

Hormones Vary Widely in Effect and

Structure
• Hormones may be soluble or insoluble in lipids
• Lipid-soluble hormones
- Usually diffuse across the plasma membrane
- And go into their target cell’s cytoplasm

• Lipid-insoluble hormones
- Are large or hydrophilic
- Do not cross the plasma membrane
- Instead bind to a receptor on the cell’s plasma membrane

Table 11.1 Hormones Have Diverse Structures and Functions

 Steps of Cell–Cell Signaling
• Cell–cell signaling occurs in four steps:
1. Signal reception
2. Signal processing
3. Signal response
4. Signal deactivation

Earl W. Sutherland discovered how

the hormone epinephrine acts on cells

Overview of cell signaling.

EXTRACELLULAR CYTOPLASM
FLUID Plasma membrane
1 Reception 2 Processing 3 Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction
pathway

Signaling
molecule

• Reception: target cell detection

• Processing: single-step or series of changes
• Response: triggering of a specific cellular response

Step 1: Signal Reception

• Signal receptors are bound by
- Hormones
- Other cell–cell signals

• The presence of an appropriate receptor protein dictates which cells

will be able to respond to a particular hormone

• Identical receptors in diverse cells and tissues

- Allow long-distance signals to coordinate the activities of cells
- Throughout a multicellular organism
Signal Receptors
• Signal receptors are
- Proteins that change their shape or activity
- After binding to a signaling molecule

• Signal receptors
- Are dynamic
- May change in their sensitivity to particular hormones
- Can be blocked

Signal Receptors
• Signal receptors that bind to lipid-soluble hormones are located inside
the cell
• Other signal receptors are located in the plasma membrane

Step 2: Signal Processing

• Lipid-soluble hormones that cross the plasma membrane produce
different cell responses than lipid-insoluble hormones that bind to
membrane receptors
 Signal Processing in Lipid-Soluble
Hormones
• Lipid-soluble steroid hormones
- Bind to receptors inside the cell
- Trigger a change in the cell’s activity directly

• The hormone–receptor complex

- Is transported to the nucleus
- Where it alters gene expression

Figure 11.12
Some Cell–Cell Signaling
1. Signal arrival
Molecules Enter the Cell Plasma Steroid
hormone
and Bind to Receptors in membrane

the Cytoplasm.

2. Signal reception
Receptor
in cytosol

Nucleus
3. Direct signal
response

Target gene DNA

Signal Processing in Lipid-Insoluble

Hormones
• Hormones that cannot diffuse across the plasma membrane bind to
membrane receptors
• When a signal binds at the cell surface, it
- Triggers a complex series of events
- Collectively called a signal transduction pathway
- Converts the extracellular hormone signal to an intracellular signal
 Signal Processing in Lipid-Insoluble
Hormones
• The message transmitted by a hormone is amplified as it changes form
• Signal transduction occurs at the plasma membrane
• Amplification occurs inside

Figure 11.13
Signal Transduction Converts Extracellular signaling
an Extracellular Signal to an Receptor protein
molecule
1. Signal reception
Intracellular Signal. in membrane

Intracellular
signaling 2. Signal
molecules transduction

3. Signal
amplification

Nucleus

4. Signal response

Target gene DNA

Signal Transduction
• Signal transduction involves G proteins or enzyme-linked receptors
• G proteins trigger the production of an intracellular messenger
• Enzyme-linked receptors trigger the activation of a series of proteins
inside the cell
G Proteins
• G proteins are
- Intracellular peripheral membrane proteins
- Closely associated with transmembrane signal receptors

• When G proteins are activated by a signal receptor trigger the

production of messengers inside the cell
• G proteins link the receipt of an extracellular signal to the production
of an intracellular signal

G Proteins
• G proteins are activated when they bind GTP
• G proteins are deactivated when they hydrolyze the bound GTP to
GDP

G Proteins and Signal Transduction

• Linking an external signal to the production of an intracellular signal
involves three steps:
1. Hormone binds to the membrane receptor
• Changes shape
• Activates G protein
2. G protein exchanges GDP for GTP
• Splits into two parts
3. One part of the G protein activates a membrane enzyme
• Catalyzes the production of a second messenger
Figure 11.14
G-Protein-Coupled Receptors Signal

Trigger the Production of a Receptor Enzyme

Second Messenger.
1. Signal received.

G protein in “off”
conformation

2. G protein binds
GTP and splits.

G protein in “on”
conformation

Enzyme

3. Activated G protein
binds to enzyme,
which produces
second messenger.
Substrate
Second messenger

Triggers response

Second Messengers
• Second messengers
- Are small molecules
- Diffuse rapidly throughout the cell
- Amplify the hormone signal

• Several second messengers work by activating protein kinases

• Kinases add a phosphate group to other proteins
- Phosphorylate

Table 11.2 Examples of Second Messengers

 Enzyme-Linked Receptors
• Enzyme-linked receptors
- Are transmembrane proteins
- Bind a hormone signal
- Directly catalyze a reaction inside the cell

• The receptor tyrosine kinases (RTKs) are the best-known group of

enzyme-linked receptors

Receptor Tyrosine Kinases and Signal

Transduction
• Directly catalyzing an intracellular reaction involves five steps:
1. Hormone binds to an RTK
2. RTK forms a dimer and is phosphorylated by ATP
3. Proteins build a bridge between RTK, and the Ras protein is subsequently
activated
4. Ras triggers the phosphorylation and activation of another protein
5. Phosphorylation cascade amplifies the original signal many times over
• Each phosphorylated protein catalyzes the phosphorylation of other proteins

Figure 11.15 Enzyme-Linked Receptors Signaling molecule

Trigger a Phosphorylation Cascade.

1. Signal received.
Receptor
Ras protein tyrosine
kinase (RTK)

2. Receptor complex
is phosphorylated.

3. Ras exchanges
GDP for GTP.
Ras Bridging
proteins

4. A protein kinase
is activated.

Inactive Active
kinase 1 kinase 1
5. Phosphorylation
cascade results.

Inactive
kinase 2 Active
kinase 2

Inactive
kinase 3
Triggers response
Results of Signal Processing
• Many of the key signal transduction events observed in cells occur via
- G proteins
- Enzyme-linked receptors

• The signal transduction event has two results:

1. Easily transmitted extracellular message is converted into an intracellular
message
2. Original message is often amplified many times over

Step 3: Signal Response

• The ultimate response to a cell–cell signal varies from signal to signal
and from cell to cell
• Falls into two general categories:
1. A change in which genes are being expressed in the target cell
2. Activate or deactivate a particular target protein that already exists in the cell

Step 4: Signal Deactivation

• Turning off cell signals is just as important as turning them on
• Cells have automatic and rapid mechanisms for signal deactivation
• These mechanisms allow the cell to remain sensitive to small changes
in
- The concentration of hormones
- The number and activity of signal receptors
Summary of Hormonal Signaling
• The end result of cell sensitivity to hormonal signaling is
- An integrated whole-organism response to changing conditions
- Occurs both inside and outside the multicellular organism

Interactions between Signaling Pathways

• Each cell
- Has many intracellular and membrane signal receptors
- Receives an almost constant stream of different chemical signals about changes
in the environment

• The signal transduction pathways

- That are triggered by these signals and receptors intersect and connect
- Form a complex network that allows cells an integrated response to an array of
extracellular signals

Crosstalk, Interactions between Signaling

Pathways
• Crosstalk integrates the diverse signals that a cell receives
• Elements or products from one pathway may affect another pathway,
ultimately affecting the overall cell response
- Can be reduced when one pathway inhibits another
- Can be increased when one pathway stimulates another
 Crosstalk, Interactions between Signaling
Pathways
• At multiple points, the cell can
- Regulate the flow of information
- Allow the cell to respond appropriately to many simultaneous signals

Figure 11.16 Pathway A Pathway B Pathway C

Signaling Pathways
Interact via “Crosstalk.”
Signaling Signaling Signaling
molecule A molecule B molecule C

Receptor A Receptor B Receptor C

A1 B1 C1

A2 B2 C2

A3 B3 C3

A4 B4 C4

Cell Cell Cell

response A response B response C

Quorum Sensing in Bacteria

• Even unicellular organisms live together and communicate with one
another
• Cell–cell communication in bacteria is called quorum sensing
• Bacteria release species-specific signaling molecules when their
numbers reach a specific threshold
• Response to the signal molecules varies across species
Figure 11.17 Unicellular Organisms Interact and Respond in a Variety of Ways.

(a) Yeast cells alter their growth in response (b) Slime mold amoebae aggregate in
to pheromones of the opposite mating type. response to sensing a quorum.

Red stain
shows new
cell growth

Cells migrate
toward a
5 m 100 m central point

Responses to Signaling in Bacteria

• Bioluminescence = light emission
• Secretion of proteins that allow the bacteria to attack multicellular
hosts cause disease
• Production and secretion of biofilms
- Hard, polysaccharide-rich substances
- Encase the cells and attach them to a surface

End of week 11
• Good luck for your health
• See you next week