Lecture 13: Fluid Mosaic Model, Membrane Proteins

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Morris: Chapter 5 sections 5.1-5.2 and figure 5.8

22 Terms

1

Cell membranes

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2

Function of biological membranes

  1. define cell boundary (organelles; mitochondria, Golgi, etc)

  2. define enclose compartments

  3. control movement of material into and out of cell

  4. allow response to external stimuli

  5. enable interactions between cells

  6. provide scaffold for biochemical activities

    1. energy transduction; mitochondria/chloroplast provides scaffolding for biochemical activities producing energy

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3

Plasma membrane

  • PM: plasma membrane

  • SR: sarcoplasmic reticulum

    • endoplasmic reticulum equivalent, movement of cations into muscle cells causing contractions

  • Red blood cells are used to study PM b/c they don’t have nuclei or internal membrane

  • Trilaminar structure made of a phospholipid bilayer

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4

Trilaminar structure

  • made of phospholipid bilayer

  • ~6nm thick

  • made up of phospholipids (phosphate head, hydrophobic tail, polar hear - inner layer)

    • micelle: formation of phospholipids into sphere shape (no lumen)

    • liposome: double phospholipid membrane layer with a lumen inside

<ul><li><p>made of phospholipid bilayer</p></li><li><p>~6nm thick</p></li><li><p>made up of phospholipids (phosphate head, hydrophobic tail, polar hear - inner layer)</p><ul><li><p><strong>micelle:</strong> formation of phospholipids into sphere shape (no lumen)</p></li><li><p><strong>liposome:</strong> double phospholipid membrane layer with a lumen inside</p></li></ul></li></ul><p></p>
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5

Phospholipids forming the plasma membrane

lipid molecules spontaneously aggregate to bury their hydrophobic tails in the interior and expose their hydrophilic heads to water

  • micelles are formed by fatty acids with only one hydrophobic tail

  • amphipathic: hydrophobic (non-polar) and hydrophilic (polar) regions

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6

Phospholipid structure

  • two fatty acid chains

  • esterified (ester bonds)

  • stereospecific (left to right) numbering sn-1 and sn-2 of the glycerol, sn-3 has head group linked by phosphate residue

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7

What attaches to the glycerol portion of phospholipid?

  • phosphatidyl-:

    • ethanolamine

    • choline

    • serine

    • inositol

<ul><li><p>phosphatidyl-:</p><ul><li><p>ethanolamine</p></li><li><p>choline</p></li><li><p>serine</p></li><li><p>inositol</p></li></ul></li></ul><p></p>
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8

Other type of phospholipid:

  • sphingolipid: mimics the shape of glycerol — has hydroxyl instead of ester

    • class of lipids containing backbone of sphingoid bases instead of glycerol which are a set of aliphatic amino alcohols

    • groups bonded to terminal oxygen:

      • phosphocholine forms sphingomyelin/SM (nervous system)

      • hydroxyl group forms a ceramide

      • glucose forms glucosesphingolipid

    • important in signal transduction and cell recognition

<ul><li><p>sphingolipid: mimics the shape of glycero<mark data-color="#ebff03" style="background-color: #ebff03; color: inherit">l —</mark><strong><mark data-color="#ebff03" style="background-color: #ebff03; color: inherit"> has hydroxyl instead of ester</mark></strong></p><ul><li><p>class of lipids containing backbone of sphingoid bases instead of glycerol which are a set of aliphatic amino alcohols</p></li><li><p>groups bonded to terminal oxygen:</p><ul><li><p>phosphocholine forms sphingomyelin/SM (nervous system)</p></li><li><p>hydroxyl group forms a ceramide</p></li><li><p>glucose forms glucosesphingolipid</p></li></ul></li><li><p>important in signal transduction and cell recognition</p></li></ul></li></ul><p></p>
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9

Phospholipid synthesis basics

  • occurs at the interface of the cytosol and outer ER (which has all the enzymes for synthesis and distribution)

  • multistep process

<ul><li><p>occurs at the <strong>interface</strong> of the <strong>cytosol and outer ER</strong> (which has all the enzymes for synthesis and distribution)</p></li><li><p>multistep process</p></li></ul><p></p>
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10

Phospholipid synthesis steps pt 1

  • cytosol: fatty acids (FA) activated by attachment of CoA molecule → activated FA bonds to glycerol phosphate into ER membrane → phosphate removed by phosphate enzyme → choline is attached via choline phosphotransferase → flippases transfer phospholipid to leaflet

    • flippases → phospholipid to inner leaflet membrane

    • floppases → phospholipids to outer leaflet membrane

<ul><li><p>cytosol: fatty acids (FA) activated by attachment of CoA molecule → activated FA bonds to glycerol phosphate into ER membrane → phosphate removed by phosphate enzyme → choline is attached via choline phosphotransferase → flippases transfer phospholipid to leaflet</p><ul><li><p>flippases → phospholipid to inner leaflet membrane</p></li><li><p>floppases → phospholipids to outer leaflet membrane</p></li></ul></li></ul><p></p>
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11

Phospholipid synthesis steps pt 2

vesicle containing phospholipids) leaves the ER for the cytoplasmic cellular membrane on the exterior leaflet (exocytosis via the 2 inner and outer membranes)

  • different cells have different cell membranes (integral, peripheral, chloroplast, glycoprotein, glycolipid)

<p>vesicle containing phospholipids) leaves the ER for the cytoplasmic cellular membrane on the exterior leaflet (<strong>exocytosis </strong>via the 2 inner and outer membranes)</p><ul><li><p>different cells have different cell membranes (integral, peripheral, chloroplast, glycoprotein, glycolipid)</p></li></ul><p></p>
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12

Fluid Mosaic Model

  • fluid: individual lipids move

  • mosaic: diverse ‘particles’ like proteins, carbohydrates, and cholestorol penetrate the lipid layer

  • proposed by Seymour Jonathan Singer and Garth Nicolson in 1972

    • 2-dimensional liquid restricting the diffusion of membrane components

      • proteins embedded in layer, are mobile, and can interact

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13

Dynamic of plasma membrane - Lipids

Lipids:

  • move easily, laterally, within leaflet

  • movement to other leaflets is slow

<p>Lipids:</p><ul><li><p>move easily, laterally, within leaflet</p></li><li><p>movement to other leaflets is slow</p></li></ul><p></p>
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14

Dynamic of plasma membrane - Membrane Proteins

  • diffuses within the bilayer

  • movement is restricted

  • rapid movement is spatially limited (small area it can move fast)

  • long range diffusion is slow

  • biochemical modification can alter protein mobility → important for signal transduction

<ul><li><p>diffuses within the bilayer</p></li><li><p>movement is restricted</p></li><li><p>rapid movement is spatially limited (small area it can move fast)</p></li><li><p>long range diffusion is slow</p></li><li><p>biochemical modification can alter protein mobility → <strong>important for signal transduction</strong></p></li></ul><p></p>
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15

Frye-Edidin Experiment (1970)

  • inspired Singer and Nicolson’s Mosaic

  • fused mouse and human cells → discover surface proteins diffuse around the unified membrane

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16

Different biological membranes

Cell plasma membranes contain combinations of glycosphingolipids, cholesterols, and protein receptors which are organized into microdomains called lipid rafts

  • microdomains can compartmentalize cellular processes by organizing centers of the assembly of signaling models -> allowing closer interactions between protein receptors and effectors to promote kinetically favorable interactions that are necessary for signal trandcution

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Example of differences in biological membranes

oligodendrocytes are types of neurons surrounded by myelin sheath:

  • myelin sheath have very few types of transmembrane protein

    • consists of layers of plasma membrane wrapping an axon

    • increases speed of electrical signals

the inner membrane of the mitochondria has a very high concentration of protein necessary for ETC and ATP synthesis

<p>oligodendrocytes are types of neurons surrounded by <strong>myelin sheath:</strong></p><ul><li><p>myelin sheath have very few types of transmembrane protein</p><ul><li><p>consists of layers of plasma membrane wrapping an axon</p></li><li><p>increases speed of electrical signals</p></li></ul></li></ul><p>the <strong>inner membrane </strong>of the mitochondria has a very high concentration of protein necessary for ETC and ATP synthesis</p>
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18

Three classes of membrane proteins

  1. integral membrane proteins spans across the lipid bilayer

    • transport nutrients/ions, cell-cell communication, attachment

  2. peripheral membrane proteins associate with the surface of the bilayer

  3. lipid-anchored proteins are attached to a lipid in the bilayer

<ol><li><p><strong>integral</strong> membrane proteins spans across the lipid bilayer</p><ul><li><p>transport nutrients/ions, cell-cell communication, attachment</p></li></ul></li><li><p><strong>peripheral</strong> membrane proteins associate with the surface of the bilayer</p></li><li><p><strong>lipid-anchored </strong>proteins are attached to a lipid in the bilayer</p></li></ol><p></p>
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19

Symmetry of biological membranes

  • asymmetrical

  • two leaflets have distinct lipid composition in many plasma membranes

    • outer contains glycolipids and glycoproteins

<ul><li><p>asymmetrical</p></li><li><p>two leaflets have distinct lipid composition in many plasma membranes</p><ul><li><p>outer contains glycolipids and glycoproteins</p></li></ul></li></ul><p></p>
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20

What changes fluidity

warmer and unsaturated lipids increase fluidity → liquid crystal

cooling and saturated lipids decrease fluidity → crystalline gel

<p><mark data-color="#fc7e7e" style="background-color: #fc7e7e; color: inherit">warmer and unsaturated lipids </mark><strong><mark data-color="#fc7e7e" style="background-color: #fc7e7e; color: inherit">increase</mark></strong><mark data-color="#fc7e7e" style="background-color: #fc7e7e; color: inherit"> fluidity → liquid crystal</mark></p><p><mark data-color="#7ef3fc" style="background-color: #7ef3fc; color: inherit">cooling and saturated lipids </mark><strong><mark data-color="#7ef3fc" style="background-color: #7ef3fc; color: inherit">decrease</mark></strong><mark data-color="#7ef3fc" style="background-color: #7ef3fc; color: inherit"> fluidity → crystalline gel</mark></p><p></p>
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21

How cholesterol modulates membrane fluidity

  • bidirectional regulator that either stabilizes/raises melting point vs intercalates the membranes

    • added to liquid crystal = fluidity decrease

    • added to crystalline gel = fluidity increase

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22

Countering temperature changing fluidity

  1. desaturation of lipids

  2. exchange of lipid chains

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