Biol219 Lecture 9 Fall 2016 Dr Scott

Permeability - the ability of a substance to pass through a are selectively permeable Permeability is determined by A. the phospholipid bilayer and B. transport in the membrane

A. Permeability through the Bilayer 1. molecular size - smaller molecules are more permeable B. Membrane Transport Proteins (channels, carriers, and pumps) - enable certain ions and polar molecules to cross the membrane 2. lipid solubility - lipid-soluble (non-polar) molecules are more permeable - polar molecules and ions do not easily cross the lipid bilayer • channels form passageways for certain ions

1 Biol219 Lecture 9 Fall 2016 Dr Scott

Permeability of the Plasma Membrane

Highly permeable Less permeable Impermeable O2 & CO 2 Na+, K+, Cl– (via channels) proteins* fatty acids , a.a.’s (via carriers) DNA & RNA steroids ATP

H2O (variable: pores) * except via membrane-bound • carrier proteins are used for certain polar molecules such as glucose vesicles

Transport Across Membranes Transport Across Membranes

1. Simple 1. Simple Diffusion - no required 2. 2. Osmosis 3. Diffusion through channels 3. Diffusion through channels 4. Protein- 5. Primary 4. Facilitated diffusion mediated 6. Secondary active transport 5. Primary active transport Active Transport Transport - requires energy 7. Transport via membrane-bound vesicles 6. Secondary active transport

2 Biol219 Lecture 9 Fall 2016 Dr Scott

Diffusion in a Solution Diffusion Across a Membrane

Diffusion occurs from high to low concentration (down a concentration gradient)

Rate of Diffusion Across a Membrane Osmosis – passive movement of water across a membrane in response to a solute concentration gradient Fick’s Law of Diffusion

Select ively-permeable me mbra ne : permeable to water, Water follows solutes; impermeable t o solut e “solutes suck”

Osmotic : force that results from the difference in concentration of solutes across the membrane

3 Biol219 Lecture 9 Fall 2016 Dr Scott

Tonicit y Osmolarity and Osmotic Pressure • effect of an extracellular solution on cell volume Ø osmosis depends on osmolarity • due to osmosis across the = total concentration of all solute particles in solut ion • depends on concentration of non-penetrating solutes only Ø 1 Osm (= 1,000 mOsm) = 1M total solute concentration Hypotonic Solution - water enters the cell by osmosis - cell gains volume (swells) (0 m Osm )

Hypertonic Solution - water leaves the cell by osmosis Ø solute concentration (osmolarity) difference results in a large osmotic pressure difference (π = CRT) - cell loses volume Ø osmotic pressure difference is the driving force for osmosis (shrinks)

Crenated RBCs in a Hypertonic Solution Isotonic Solution - concentration of non-pen etrati n g so l utes i s equal in the ECF and ICF

- no net water movement IC F EC F by osmosis - cell volume remains 300 mOsm 300 mOsm constant

Example: 0.9% NaCl (0.9 g/dL) (“normal saline”)

Image: Copyright © 2004 Dennis Kunkel Microscopy, Inc.

4 Biol219 Lecture 9 Fall 2016 Dr Scott

Transport Across Membranes Protein- channels, carriers, and pumps

1. Simple Diffusion Passive Transport - no energy required 2. Osmosis 3. Diffusion through channels Protein- 4. Facilitated diffusion mediated 5. Primary active transport Active Transport Transport - requires energy 6. Secondary active transport

Diffusion Through Channels

5 Biol219 Lecture 9 Fall 2016 Dr Scott

Diffusion of ions is influenced by both Electrical force on ions is due to chemical and electrical driving forces. which results from slight imbalance of + and – charges between the ICF and ECF (more negative inside).

No membrane potential – chemical force only (outward for K+, inward for Na+)

Membrane potential present – chemical and electrical forces =

For K+, chemical and electrical gradients are in the opposite direction (chem. outward, elec. inward), so the electrochemical gradient is small.

For Na+, chemical and electrical gradients are in the same direction (both inward), so the electrochemical gradient is large The combined force is the electrochemical gradient.

Facilitated Diffusion

6 Biol219 Lecture 9 Fall 2016 Dr Scott

Facilitated Diffusion Carrier-mediated transport exhibits saturation. The transport maximum depends on the number of GLUT transporters carrier proteins present in the membrane. - mediate transport of glucose into most cells

- the GLUT4 transporter in skeletal muscle and adipose tissue is activated by insulin

Primary Active Transport Mechanism of the Na+-K+ ATPase - Transports molecules The sodium-potassium pump against a gradient (Na+-K+-ATPase) - Uses energy from ATP directly

7 Biol219 Lecture 9 Fall 2016 Dr Scott

Secondary Active Transport

- Transports molecules against their gradient - Uses potential energy stored in ionic gradients (energy supplied indirectly by ATP ) - Involves coupled transport with an ion moving “downhill”

The sodium-glucose (SGLT) transporter

Mechanism of the SGLT Transporter

8 Biol219 Lecture 9 Fall 2016 Dr Scott

Vesicular Transport

– Vesicles created by the cytoskeleton

– Cell engulfs bacterium or other particle into phagosome

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Figure 5.18 Phagocytosis Slide 1 Slide 2 Figure 5.18 Phagocytosis

Ba c te rium Ba c te rium

The phagosome containing Phagocyte the bacterium separates Phagocyte Lysosome from the cell membrane and Lysosome moves into the cytoplasm.

The phagocytic white blood The phagocytic white blood cell encounters a bacterium The phagosome fuses wi th cell encounters a bacterium that binds to the cell lysosomes containing that binds to the cell membrane. digestive enzymes. membrane.

The phagocyte uses its The bacterium is killed cytoskeleton to push its and digested wi th i n the cell membrane around the vesicle. bacterium, creating a large vesicle, the phagosome.

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9 Biol219 Lecture 9 Fall 2016 Dr Scott

Slide 3 Figure 5.18 Phagocytosis Slide 4 Figure 5.18 Phagocytosis

Ba c te rium Ba c te rium

The phagosome containing Phagocyte Phagocyte the bacterium separates Lysosome Lysosome from the cell membrane and moves into the cytoplasm.

The phagocytic white blood The phagocytic white blood cell encounters a bacterium cell encounters a bacterium that binds to the cell that binds to the cell membrane. membrane.

The phagocyte uses its The phagocyte uses its cytoskeleton to push its cytoskeleton to push its cell membrane around the cell membrane around the bacterium, creating a large bacterium, creating a large vesicle, the phagosome. vesicle, the phagosome.

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Figure 5.18 Phagocytosis Slide 5 Figure 5.18 Phagocytosis Slide 6

Ba c te rium Ba c te rium

The phagosome containing The phagosome containing Phagocyte the bacterium separates Phagocyte the bacterium separates Lysosome from the cell membrane and Lysosome from the cell membrane and moves into the cytoplasm. moves into the cytoplasm.

The phagocytic white blood The phagocytic white blood cell encounters a bacterium The phagosome fuses wi th cell encounters a bacterium The phagosome fuses wi th that binds to the cell lysosomes containing that binds to the cell lysosomes containing membrane. digestive enzymes. membrane. digestive enzymes.

The phagocyte uses its The phagocyte uses its The bacterium is killed cytoskeleton to push its cytoskeleton to push its and digested wi th i n the cell membrane around the cell membrane around the vesicle. bacterium, creating a large bacterium, creating a large vesicle, the phagosome. vesicle, the phagosome.

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10 Biol219 Lecture 9 Fall 2016 Dr Scott

Extracellular fluid Vesicular Transport Ligand binds to membrane receptor. Re c e ptor-ligand migrates to clathrin-coated pit.

Transport vesicle and cell membrane Cla thrin-coated fuse (membrane pit • Endocytosis re c y c ling).

– Membrane surface indents and forms vesicles Re c e ptor

– Active process that can be nonselective Cla thrin () or highly selective Vesicle loses Transport vesicle clathrin coat. wi th re c e p to rs m o v e s – Receptor-mediated endocytosis uses coated pits to the cell membrane.

• Clathrin most common protein in coated pits Re c e ptors and ligands To lysosome or separate. Go l g i c o m p l e x

– Membrane recycling Endosome Ligands go to lysosomes or Golgi for processing. Intracellular fluid © 2016 Pearson Education, Inc.

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Extracellular fluid Extracellular fluid Ligand binds to membrane receptor. Ligand binds to membrane receptor.

Re c e ptor-ligand migrates to clathrin-coated pit.

Cla thrin-coated pit

Re c e ptor Re c e ptor

Cla thrin

Intracellular fluid Intracellular fluid © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc.

11 Biol219 Lecture 9 Fall 2016 Dr Scott

Extracellular fluid Extracellular fluid Ligand binds to membrane receptor. Ligand binds to membrane receptor.

Re c e ptor-ligand migrates to clathrin-coated pit. Re c e ptor-ligand migrates to clathrin-coated pit.

Cla thrin-coated Cla thrin-coated Endocytosis Endocytosis pit pit

Re c e ptor Re c e ptor

Cla thrin Cla thrin

Vesicle loses clathrin coat.

Intracellular fluid Intracellular fluid © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc.

Extracellular fluid Extracellular fluid Ligand binds to membrane receptor. Ligand binds to membrane receptor.

Re c e ptor-ligand migrates to clathrin-coated pit. Re c e ptor-ligand migrates to clathrin-coated pit.

Cla thrin-coated Cla thrin-coated Endocytosis Endocytosis pit pit

Re c e ptor Re c e ptor

Cla thrin Cla thrin

Vesicle loses Vesicle loses clathrin coat. clathrin coat.

Re c e ptors Re c e ptors and ligands and ligands separate. To lysosome or separate. Go l g i c o m p l e x

Endosome Endosome Ligands go to lysosomes or Golgi for processing. Intracellular fluid Intracellular fluid © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc.

12 Biol219 Lecture 9 Fall 2016 Dr Scott

Extracellular fluid Extracellular fluid Ligand binds to membrane receptor. Ligand binds to membrane receptor.

Re c e ptor-ligand migrates to clathrin-coated pit. Re c e ptor-ligand migrates to clathrin-coated pit.

Transport vesicle Cla thrin-coated and cell membrane Cla thrin-coated Endocytosis fuse (membrane Endocytosis pit pit re c y c ling).

Re c e ptor Re c e ptor

Cla thrin Cla thrin

Vesicle loses Vesicle loses Transport vesicle clathrin coat. Transport vesicle clathrin coat. wi th re c e p to rs m o v e s wi th re c e p to rs m o v e s to the cell membrane. to the cell membrane.

Re c e ptors Re c e ptors and ligands and ligands To lysosome or separate. To lysosome or separate. Go l g i c o m p l e x Go l g i c o m p l e x

Endosome Endosome Ligands go to lysosomes Ligands go to lysosomes or Golgi for processing. or Golgi for processing. Intracellular fluid Intracellular fluid © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc.

Epithelial Transport

• Apical (mucosal) membrane • Basal membrane • Paracellular transport – Through junctions between adjacent cells • – Through cells themselves – with vesicular transport

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13 Biol219 Lecture 9 Fall 2016 Dr Scott

Figure 5.20 Transporting Epithelial Transport epithelia are polarized

• Absorption from lumen to extracellular fluid Lumen of intestineor kidney (ECF) Apical membrane wi th microvilli faces the lumen. Tra ns porting • Secretion from ECF to lumen epithelial cell limits Tight junction Abs orption (transcellular) movement of substances between the cells.

• Transcellular transport of glucose uses Tra ns port proteins Abs orption (paracellular) membrane proteins Bas olateral membrane faces the ECF.

Extracellular fluid

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Figure 5.21 Transepithelial absorption of glucose Transepithelial Transport of Water

[Glucose]low Gl u Na + [Na +]high Lumen of kidney or intestine Na +-glucose brings glucose into cell against its gradient using energy stored in the Na + concentration gradient.

Apic a l membrane GLUT transporter transfers glucose to ECF by facilitated diffusion.

[Glucose]high Gl u Na + [Na +]low

Na +-K+-ATPase pumps Active transport Osmosis: Epithelial Na + out of the cell, keeping of solutes into lateral H2O follow solute + cell ICF Na concentration low. int ercellular space mov e me nt

Ba s ola te ra l FIGURE QUESTIONS membrane Gl u Na + K+ 1.Ma t c h each transporter to its location. Choos e either 1. GL UT (a)apical membrane 2. Na +-glucose symporter (b)basolateral + + ATP 3. Na -K -ATPase membrane 2. Is glucose mo v em en t ac r o ssthe Extracellular basolateral me mb r a ne ac t i ve or fluid passive? Explain. 3. Why doesn't Na+ movement at the ap i ca l + Na + K+ [Glucose]low Gl u [Na ]high membrane re quireATP?

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