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Signal Transduction: Signal Transduction:

Signal Transduction: - PowerPoint Presentation

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Signal Transduction: - PPT Presentation

LigandReceptor Interactions Cell and Developmental Biology Group Goals Integration of quantitative skills in cell biology Modeling cellular responses   Class setup First or second year majors in cell biology ID: 569195

ligand µm receptor response µm ligand response receptor affinity threshold cellular 000 cell graph curves adrenaline high 100 heart battery blood complexes

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Slide1

Signal Transduction:

Ligand-Receptor Interactions

Cell and Developmental

Biology GroupSlide2

Goals –

Integration of quantitative skills in cell biology

Modeling cellular responses

 Slide3

Class setup

First or second year majors in cell biology

Co-requisite with Calculus

Middle of the course

~1 hour lecture

Learning outcomes

1) Relate the concept of threshold to cellular responses

2) Understand how these components affect threshold

- ligand and receptor concentrations

- binding affinity

3) Apply knowledge of quantitative models of cellular responseSlide4

A driver returned to his car after a 3 hour shopping spree to see the following sight. His car would not start. Why?Slide5

Battery current thresholds

Battery power

0%

100%Slide6

Draw how the battery / ignition threshold would look on this graph

Battery current

Response (ignition)

low

high

No ignition

ignitionSlide7

Cell Signaling

EXTRACELLULAR

FLUID

Reception

Receptor

Signal

molecule

Plasma membrane

Transduction

CYTOPLASM

Relay molecules in a signal transduction

pathway

Response

Activation

of cellular

response

Tomorrow’s presentationSlide8

What happens when you see this?Slide9

Effects of adrenaline on different tissues in the bodySlide10

Threshold as it relates to ligand

receptor binding and cellular function

Basic response threshold

Maximum response threshold

[Adrenaline]

Fight - Flight response

low

high

Ligand / receptor concept

ReceptionSlide11

1 Ligand receptor complex

100 - 1000 Ligand receptor complexes

1000 -10,000 Ligand receptor complexes

10,000 -100,000 Ligand receptor complexes

100,000 - 1 million Ligand receptor complexes

How many

ligand

/ receptor complexes are required to elicit a cellular response?Slide12

Binding Affinity

[L] + [R] [LR]

Dissociation Constant (K

d

): is the free ligand concentration at which 50% of receptor is occupied.

Affinity

is defined by the association constant (K

a

) =1/K

d

Each ligand / receptor complex has its own specific binding affinity.

k

1

k

-1

K

d

=

k

-1

/ k

1Slide13

[ligand]

response

Which graph represents a cell with a receptor with the highest affinity?

low

high

A

B

C

DSlide14

(Think-Pair  1 minute essay)

What is the relationship between affinity and threshold?

[ligand]

response

low

high

A

B

C

DSlide15

Affinity and the curves

 

Which of these factors can the cell control?

How might a cell be able to control its own threshold?

Affinity = 1 / K

dSlide16

Affinity and the curves

 

[Ligand]

Response

Affinity = 1 / K

d

Associate each of the following with the appropriate graph above

A. [L]=1 µM, [R]=0.5 µM, K

d

=.25 µM

[L]=1 µM, [R]=1.25 µM, K

d

=.25 µM

B

ASlide17

Affinity and the curves

 

[Ligand]

Response

Affinity = 1 / K

d

Associate each of the following with the appropriate graph above

A. [L]=1 µM, [R]=1.25 µM, K

d

=.25 µM

B. [L]=1 µM, [R]=1.25 µM, K

d

=.5 µM

A

BSlide18

Relationship between [R],[LR],Kd

In general,

What happens to [LR] when [R] increases and K

d

stays the same?

What happens to [LR] when K

d increases and [R] stays the same?Slide19

Affinity and the curves

 

[Ligand]

Response

Associate each of the following with the appropriate graph above

A. [L]=1 µM, [R]=0.5 µM, K

d

=.25 µM

[L]=1 µM, [R]=1.25 µM, K

d

=.25 µM

[L]=1 µM, [R]=1.25 µM, K

d

=.5 µM

Affinity = 1 / K

d

B

A

CSlide20

Affinity and the curves

 

[Ligand]

Response

Associate each of the following with the appropriate graph above

A. [L]=1 µM, [R]=0.5 µM, K

d

=.25 µM

[L]=1 µM, [R]=1.25 µM, K

d

=.25 µM

[L]=1 µM, [R]=1.25 µM, K

d

=.5 µM

Affinity = 1 / K

d

B

C

ASlide21

Think-Pair-Share (2 minutes)

Assume the order of response events to an adrenaline spike is:

1st) heart rate increase,

2nd) blood vessel constriction,

3rd) sweating

[ligand]

response

low

high

Which of the following associates the response curves with the physiological response?

Heart = blue,

blood = black,

sweat = green

B) Heart = green,

blood = black,

sweat = blue

C) Heart = black,

blood = blue,

sweat = green

D) All tissues would have the same response curveSlide22

What happens when your

adrenaline rush goes away?

?Slide23

Off-switch (negative threshold

)

Basic response threshold

Maximum response threshold

[Adrenaline]

Fight - Flight response

low

highSlide24

Ligand-receptor interactions are widespread and

have varied roles in organisms.

The immune system

Development

Environmental sensingSlide25

1 Ligand receptor complex

100 - 1000 Ligand receptor complexes

1000 -10,000 Ligand receptor complexes

10,000 -100,000 Ligand receptor complexes

100,000 - 1 million Ligand receptor complexes

How many

ligand

/ receptor complexes are required to elicit a cellular response?Slide26

Summative Assessment

Explain the concept of threshold

Relate changes in dissociation constants to cellular responses

Correlate changing

K

d

values to how they affect the graph

3) Describe the effects that drug A would have on the fight or flight response if drug A:

Lowered the concentration of adrenaline

Blocked the receptor

4)Relate the importance of understanding mathematics to experimentally analyzing cellular responses