membranes: keeping things where they belong separate functional and anatomic fluid compartments in...

Membranes: Keeping things where they belongMembranes: Keeping things where they belong

• Separate functional and anatomic fluid compartments in the body.

• Regulate the transport of materials between compartments

Connections between plasma membranesConnections between plasma membranes

• Extracellular matrix: primarily secreted by fibroblasts.– Collagen: forms cable-like fibers that provide tensile strength; especially

important in skin and blood vessels.*Scurvy: in vitamin C deficiency these fibers are not properly formed.

– Elastin: rubber-like protein where elasticity (ability to return to pre-stress orientation) is important; especially important in arteries and lungs.

– Fibronectin: promotes cell-cell adhesion and can hold cells in position.

Adjacent intestinal epithelial cells

Intracellular

Extracellular

Transmembrane Proteins

Tight Junctions


• Tight junctions: zona occludens– Impermeable (usually) connectio

– ns between cells.

– Cell membranes are attached to each other by strands of junctional proteins.

• Extracellular matrix

Intercellular filaments(commonly glycoproteins)

Intracellular keratin filaments

Thickened “plaque” area

SpotDesmosome

Intracellular

Extracellular


• Spot desmosomes: macula adherens (~20 nm)– anchor cells together with some space to accommodate

movement/stretching.• Cytoplasmic plaque

• Intracellular intermediate filaments through cells connecting various plaques

• Intercellular glycoprotiens connect the cells


• Tight junctions: zona occludens

Gap Junctions

Intracellular

Extracellular

Connexons

1.5 nm

Passage of ionsAnd small molecules

Large moleculesblocked


• Gap Junctions: no fancy latin name; 2-4 nm– Communication between cells through connexons

– Permit passage of small ions and particles between cell's cytoplasm


• Tight junctions: Tight junctions: zona occludens

• Spot desmosomes: macula adherens

Membrane TransportMembrane Transport

• Passive: movement of material without the expenditure of energy.– Simple Diffusion

• particles in random motion display net movement relative to two conditions

– Chemical gradient: material moves "down" it's concentration gradient.


• Passive: movement of material without the expenditure of energy.– Simple Diffusion

• particles in random motion display net movement relative to two conditions

– Chemical gradient: material moves "down" it's concentration gradient.

* Osmosis: the movement of water "down" it's concentration gradient.

*Osmotic pressure: a "negative" effective pressure that acts to "pull" water

Semi-permeable

X m

mH

g

X mmHg


Passive: movement of material without the expenditure of energy.

• Simple Diffusion– particles in random motion display net movement relative to two driving force

conditions• Chemical gradient: material moves "down" it's concentration gradient.

• Ionic charge: electrical attaction/repulsion

– Other factors influencing volume-rate diffusion• Permeability of the membrane to the substance

– Lipid-soluble-passes through

– Water-soluble - generally require selective channels or pores

• Molecular weight of the substance

• Surface area

• Distance (thickness of the membrane)

• Facilitated (carrier-mediated) diffusion - the diffusion of the material occurs via specialized protein "carriers"



• Simple diffusion

• Facilitated (carrier-mediated) diffusion - the diffusion of the material occurs via specialized protein "carriers"

– particles in random motion display net movement relative to their electrochemical gradient

– Display unique characteristics• Specificity: only one molecule (or class of molecules) transported

• Saturation: The rate of transport of molecules is limited to the number of carriers.There are only so many lifeboats on the Titanic

• Competition: When the carrier can transport multiple forms of a molecule (or drugs that closely resemble the molecule), the multiple forms compete for the limited number of carriers.

If a ferry has 100 seats, and 70 are occupied by women, ony 30 men are getting across.




• Facilitated (carrier-mediated) diffusion

Active Transport: requiring the expenditure of energy

• Primary: Energy used directly in transport of the molecule(s)







– Typical series of events• ATP is used to phosphorylate the carrier

– carrier becomes exposed to the side with low concentration of the molecule to be transported

– Increased affinity for the transported molecule

• Binding of the molecule usually causes conformational (structrural) change– Molecule is exposed to high concentration side

– Carrier is dephosphorylated

– Affinity for the molecule decreases, and the molecule is released

– Simple design: one molecule (or class), one direction

– Complex designs: multiple molecules; mutiple directions

Membrane TransportMembrane TransportPassive: movement of material without the expenditure of energy.• Simple diffusion• Facilitated (carrier-mediated) diffusion

Active Transport: requiring the expenditure of energy • Primary: Energy used directly in transport of the molecule(s)

– Typical series of events• ATP is used to phosphorylate the carrier

– carrier becomes exposed to the side with low concentration of the molecule to be transported– Increased affinity for the transported molecule

• Binding of the molecule usually causes conformational (structrural) change– Molecule is exposed to high concentration side– Carrier is dephosphorylated– Affinity for the molecule decreases, and the molecule is released

– Simple design: one molecule (or class), one direction

– Complex designs: multiple molecules; mutiple directions

• Counter-transport: multiple molecules, opposite direction (3Na+/2K+)

• Co-transport: multiple molecules, same direction (not common)

• Secondary: Potential energy of another molecule used (commonly Na+)

Membrane TransportMembrane TransportPassive: movement of material without the expenditure of energy.





• Secondary: Potential energy of another molecule used (commonly Na+)

• Counter-transport: multiple molecules, opposite direction (Na+/H+)

• Co-transport: multiple molecules, same direction (Na+/Glucose)

• Vesicular– Clathrin "coated pit" pathway

• Endocytosis

• Exocytosis

– Potocytosis- the caveolae pathway• Specialized caveolin-rich "pit" in membranes with cholesterol-stabilized constituents

• Sometimes maintains "tether" connection to the membrane

• Involved in many receptor-mediated communication processes

Membrane PotentialMembrane Potential

Membrane PotentialMembrane PotentialAn electrical potential caused by unbalanced distribution (in/out) of cations

and anions. – All cells

– Can primarily be attriubuted to• Na/K exchange pump: pumps more cations out than anions in.

• Differences in permeability to Na and K: cell is much more permeable to K than to Na; the concentration gradient (K our) is balanced by the attraction of anions inside.

• Membrane impermeable anionic proteins

Membrane PotentialMembrane PotentialAn electrical potential caused by unbalanced distribution (in/out) of cations

and anions. – All cells

– Can primarily be attriubuted to• Na/K exchange pump: pumps more cations out than anions in.

• Differences in permeability to Na and K: cell is much more permeable to K than to Na; the concentration gradient (K our) is balanced by the attraction of anions inside.

• Membrane impermeable anionic proteins

– Uses of the membrane potential:• Communication via electrical transmission - primarily nerve and muscle

• Secondary energy source for transport

Cellular CommunicatonCellular Communicaton

Autocrine

Endocrine

Neural

Communications Ligand-receptor mediation


• Gated Channels- receptor activation "opens" channels for ions to move– Electrical potential transmission

– Ions controlling secretion (eg: Ca)

• Second-messenger systems– G-protein coupled

GDPGDP

β γα E1E2

GTP

β γ

GTPα

E1E2GDPGDP

β γα






• General Scheme:– Inactive: alpha,beta, and gamma subunits together; GDP bound

– Binding of GTP to alpha subunit activates; alpha +/- beta:gamma subunits alter activity of an effector molecule (kinase or phsphatase)

– Hydrolysis of GTP to GDP inactivates the G protein subunits

*Inactivation of G-protein does not necessarily inactivate effector. Thus, the chemical half-life and biological half-life are often very different.

*The same second messenger can cause different responses in different cells

ACβ γ αs

GTP

ATPcAMP

GDPGDP

PKA

Phosphorylate specific protein

βγ

αi

ADPADP

adenosine

Beta-adrenergicreceptor

epinephrine

αs

Adenylyl Cyclase






• General Scheme

• Examples:– Adenylyl Cyclase

» Gs-alpha stimulates AC to enzymatically form cyclic-AMP from ATP

» cAMP activates protein kinase A, which in turn, phosphosylates a target protein

» Degradation of cAMP to AMP may overwhelm th ability to re-phosphorylate; adenosine is produced

» Adenosine activates an inhibitory G-protein which inhibits AC- negative feedback control

PKCPLCβ γ αs

Phosphorylatespecific protein

αs

PIP2

IP3

DAG

Ca++

Signals the release of Calcium from ER



• Gated Channels- receptor activation "opens" channels for ions to move– Electrical potential transmission– Ions controlling secretion (eg: Ca)


• General Scheme• Examples:

– Adenylyl Cyclase

» Gs-alpha stimulates AC to enzymatically form cyclic-AMP from ATP

» cAMP activates protein kinase A, which in turn, phosphosylates a target protein

» Degradation of cAMP to AMP may overwhelm th ability to re-phosphorylate; adenosine is produced

» Adenosine activates an inhibitory G-protein which inhibits AC- negative feedback control

– Phosphatidylinositol isphosphate (PIP2)

» Gs-alpha activates phospholipase C (PLC)

» PLC cleaves PIP2 inot inositol-triphosphate (IP3) and diacylglycerol (DAG)

» IP3 causes the release of intracelular Ca

Calmodulin is activated by binding with Ca

Activated calmodulin then activates or inhibits other proteins

» DAG acts as a separate second messenger (often protein kinase C [PKC]).

OH-

Caspases

Apoptosis

Direct hydrolysis

Activation of other systems

?

Cell DeathEnd of the roadCell DeathEnd of the road

• Necrosis: usually associated with ischemia or abrupt damage: – Disorganized; loss of membrane integrity– Cell swelling and rupture; lysosomal enzymes released– Inflammatory response

• Apoptosis: ordered death– Activation of Caspases by

• mitochondrial cytochrome release• second messenger system• transcriptional regulation

– Caspases activate other caspases and addtional hydrolytic enzyme systems; cleave cellular components into organized fragments for disposal

membranes: keeping things where they belong separate functional and anatomic fluid compartments in...

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movement of material

concentration gradient

net movement relative

movement of water

nmanchor cells

plasma membranesgap

random motion

simple diffusionparticles