membrane structure and function - class...

Membrane Structure and Function

All Membranes are semipermeable

Proteins can move about the membrane – not a static structure

Fluid Mosiac Model

04-27-16: Lecture 9

http://www.youtube.com/watch?v=Qqsf_UJcfBc

Membrane Structure and FunctionFundamental unit is phospholipid

All Membrane are semipermeable

Proteins can move about the membrane – not a static structure

Fluid Mosiac Model Proteins move back and forth

Proteins inside the lipid bilayer should have non-polar side chains (R groups)

Interactions with hydrophobic interior

Importance of Fluidity

Adjust the fluidity by changing the degree of saturation

Cholesterol is also helpful in maintaining fluidity

It allows some substances to cross it more easily than others

04-27-16: Lecture 9


Fission of Membranes Fusion of Membranes

Examples:

Vesicle from ER fusing to Golgi

fertilization

Virus infection

Exocytosis

Examples:

Cell Division (cytokinesis)

Endocytosis

Vesicle leaving ER or leaving Golgi

04-27-16: Lecture 9

Membrane Interaction – an Up-close view


Apposition Hemifusion Full fusion(content mixing)

04-27-16: Lecture 9

Membrane Interaction – an Up-close view


Hemifusion SeparationInvagination

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Endocytosis

Brings nutrients into the cell

Brings signals into the cell

Invagination of the plasma membrane - Vesicle fission

Phagocytosis Brings foods into cell vesicle lysosome (digested)

Pinocytosis Brings soluble components into cell water vacuole

04-27-16: Lecture 9

Receptor mediated Endocytosis


Involves proteins in plasma membrane – called a receptor

transmembrane

Binds a molecule (ligand) on the outside of the cell (e.g. sugar)

Clusters on cell surface – a pit is formed

Then coated pits formed – by attachment of clathrin (a protein) inside cell

Invagination form vesicle coat falls off vesicle can go to its destination

04-27-16: Lecture 9

0.25 µm

RECEPTOR-MEDIATED ENDOCYTOSIS

Receptor

Ligand

Coat protein

Coatedpit

Coatedvesicle

TransmissionEM of a coated

pit

Plasmamembrane

Coatprotein

Receptor mediated Endocytosis


•Ligand•

•Receptor

•Receptors cluster

•Invagination

•Recruit clathrin (coat protein)

•Pinch off vesicle (fission)

•Clathrin falls off

Endocytosis

04-27-16: Lecture 9

Permeability of Membranes

Most permeable:

CO2, CH4, O2

Least permeable:

Sugars, amino acids, proteins

Membrane Structure and Function04-27-16: Lecture 9

Diffusion Rate of diffusion is proportional to concentration of a solute

Osmosis is the diffusion of water across a selectively permeable membrane

Isotonic solution: equal concentrations

Hypertonic solution: cell in a solution w/ higher solute concentration

Hypotonic solution: cell has greater solute conc than solution.

04-27-16: Lecture 9

Diffuson

Net diffusion Net diffusion Equilibrium

One solute

Net diffusion

Net diffusion

Net diffusion

Net diffusion Equilibrium

Equilibrium

Two solutes

04-27-16: Lecture 9


Integral membrane Proteins – example of structure

Types of proteins that reside at membranes

Figure 7.8

N-terminus

C-terminus

a HelixCYTOPLASMICSIDE

Extracellular side

Note: N-term (amino) and C-term (carboxyl) can be on either side and same side depending how the protein is inserted into membrane

04-27-16: Lecture 9


Integral membrane Proteins

•Penetrate the hydrophobic core

Peripheral Proteins

•Loosely bind to plasma membrane

•Typically by interacting with integral membrane proteins

Types of proteins that reside at membranes

•Some peripheral proteins can partially embed in plasma membrane

~20 a.a

•Transmembrane – span the entire lipid bilayer - ~10-20 amino acids in length

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Integral membrane Proteins Six major functions

ATP

Enzymes

Signal

1. Transport

2. Enzymatic Activity

3. Signal Transduction


Integral membrane Proteins Six major functions

4. Cell Recognition

5. Intercellular joining

6. Attachment of the cytoskeleton to the extracellular matrix

Glyco-

protein


Internal Cytoskeleton

•Microtubules (MT)

•Microfilaments (MF)

•Intermediate filaments

Polymers of tubulin

Polymers of actin

Polymers of keratin

4˚ structure : protein-protein interactions which make long chains

•Cell shape

•Rigidity/flexibility

•Transport “roadway”

•Movement

•Non-covalent

04-27-16: Lecture 9


•Microtubules

•Cell Shape (compression-resisting)

•Cell motility

•Chromosome movement in cell division

•Organelle movement (vesicle movement thru endomembrane system)

•Microfilaments

•Cell Shape (tension-bearing)

•Cell shape changes!

•Cell motility

•Muscle contraction

•Cell Division

•Intermediate filaments

•Cell Shape (tension-bearing)

•Organelle anchorage

04-27-16: Lecture 9

Cytoskeleton04-27-16: Lecture 9


Microtubules: cell transport and motility

•Central assembly point for MT in the cell is called the centrosome (MT organizing center)

•Motor proteins move along MT

•Kinesin move things away from the nucleus

•Dynein move things towards the nucleus

•Cell motility – Flagella, or cilia – use Dynein motor

04-27-16: Lecture 9

Show Kinesin Animation

Show Kinesin Animation

See Video links on website : neuron migration


Microfilaments: cell shape and motility

•Changes in cell shape is related to motility

•Three types of cell shape

•Microvilli – projections on surface –increase surface area

•Lamellipodia – membrane ruffles help sense environment – and direct movement

•Filopodia – like microvilli but less stable – also sense environment (can turn into lamellipodia)

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Actin-based motility – Filopodia and LammellipodiaGrowth cone of a neuron

5 uM

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Betz et al., 2009See Video links on website : neuron migration

Actin-based motility

Actin polymerization at the leading edge (lamellipodia)

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Actin-based motility – neuron migrating past another neuron

04-27-16: Lecture 9

See Video links on website : neuron migration

Linking the Extracellular Matrix (ECM) to the Cytoskeleton – SUPPORT!

ECM made of:•Glycoprotein (proteins modified with sugars)

•collagen (most predominant)

•Proteoglycans

•fibronectin

Collagen

Fibronectin

Plasmamembrane

EXTRACELLULAR FLUID

Micro-filaments

CYTOPLASM

Integrins

Polysaccharidemolecule

Carbo-hydrates

Proteoglycanmolecule

Coreprotein

Integrin

Figure 6.29

A proteoglycan complex

Plus Integrin (integral membrane protein)

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Linking the Cells together by Cytoskeleton – Why?

Fluid Mosaic Model •proteins are not stationary - THEY MOVE in the MEMBRANE

Tight Junction: Physical Barrier to proteins

•Link neighboring cells together so componentsCan’t get thru.

•Anchored by cytoskeleton

•Have to send proteins to the right membrane surface

•Barrier to movement in membrane

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04-27-16: Lecture 9

Moving molecules across a membrane: Transport

•Small and nonpolar molecules can freely diffuse across membrane (CO2, O2, etc)

•Protein dependent diffusion

•Facilitated Diffusionchannel protein through which small molecules (such as water) can pass.

Carrier protein - integral membrane protein switches between 2 conformation states – moving molecules across as the shape of protein changes

04-27-16: Lecture 9

Diffusion: Entropy at work - molecules move from high to low concentration

•Movement in Both directions – WHY?•Depends on the concentration gradient!!

Figure 7.15

EXTRACELLULARFLUID

Channel protein SoluteCYTOPLASM

Facilitated Diffusion

•Example of a channel protein

•Example of a carrier protein

Figure 7.15

Carrier protein Solute

-

Moving molecules across a membrane: Transport04-27-16: Lecture 9

Facilitated Diffusion


Rate

of

trans

port

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Active Transport

•A way to concentrate molecules in the cell – against conc. Gradient

•Involves a transporter or pump

•Uses Energy

•Primary active transport

•Uses ATP as energy (ATP ADP + Pi)•Conformational change in pump due transfer of phosphate to protein (phosphorylation)

•Secondary Active transport•Energy is provided by a concentration gradient•Co-transporter protein

•Example: Sugar-H+ pump which moves high of H+ and sugar together

:transport of a molecule against its concentration gradient

Don’t forget Allosteric regulation!

Previously made using ATP!

04-27-16: Lecture 9

Cell Signaling

Phosphorylation: Why is it important in signaling?

OHSerineThreonineTyrosine

+ HO P

O

O-

O-

from ATP

H20

Enzyme(Kinase)

O P

O

O-

O-

04-27-16: Lecture 9


Active Transport

•Primary active transport•Example – Sodium-Potassium Pump!!

•Sodium-Potassium Pump exchanges sodium (Na+) for potassium (K+) across the plasma membrane

•Membrane Potential•Voltage across their plasma membranes

•Voltage – is electrical potential energy – separation of opposite charges

•Cytoplasm of cells is negative compared to extracellular fluid•Unequal distribution of cations and anions

•Membrane potential is like a battery that effects the traffic of all charged molecules.

•Cell is negative so this membrane potential helps to drive transport of cations into cell

•ELECTROCHEMICAL GRADIENT – two forces: chemical and electrical


04-27-16: Lecture 9

Sodium-Potasium Pump: Maintenance of membrane potential

Na+ binding stimulatesphosphorylation by ATP.2

Na+

Cytoplasmic Na+ binds tothe sodium-potassium pump.1

K+ is released and Na+

sites are receptive again; the cycle repeats.

3 Phosphorylation causes the protein to change its conformation, expelling Na+ to the outside.

4

Extracellular K+ binds to the protein, triggering release of the Phosphate group.

6Loss of the phosphaterestores the protein’s original conformation.

5

CYTOPLASM

[Na+] low

[K+] high

Na+

Na+

Na+

Na+

Na+

PATP

Na+

Na+

Na+

P

ADP

K+

K+

K+

K+ K+

K+

[Na+] high

[K+] low

04-27-16: Lecture 9

Resting MembranePotential

Mechanism of a Action Potential

04-27-16: Lecture 9

Depolarization – initial phase of an action potentialNa+ rushes in to make inside of cell more positive

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Repolarization – later phase of the action potentialK+ (potassium rushes out) Restore resting membrane potential

Na+ and K+ channels are voltage gated – meaning they open and close at specific membrane potentials!!

04-27-16: Lecture 9

Propagation of the Action Potential

Along an axon

Afterwhich the sodium-potasium pump restores high K+/low Na+ inside and high Na+/low K+ outside

04-27-16: Lecture 9


Active Transport

•Secondary Active transport


Figure 7.19

Proton pump

Sucrose-H+

cotransporter

Diffusionof H+

Sucrose

ATP H+

H+

H+

H+

H+

H+

H+

+

+

+

+

+

+–

–

–

–

–

–

04-27-16: Lecture 9


ATP

Active TransportPassive Transport

Diffusion Facilitated Diffusion

04-27-16: Lecture 9

membrane structure and function - class...

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