Plasma Membrane

Chapter 13: The Plasma Membrane P529-P565

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Structure of Plasma Membrane

Fluid mosaic model

Lipid Bilayer
- Forms a stable barrier between two
aqueous compartments;
- Impermeable to water-soluble molecules including ions and most biological
molecules;
- The bilayer lipids are mobile, not solid.

Proteins
- Selective transport of molecules;
- Cell-cell, Cell/Matrix interactions;
- Cell signaling.

Lipid Bilayer
The outer leaflet and inner leaflet are asymmetrical
PC

SM

Outer leaflet:
SM & PC, GlycoLipid, cholesterol
Inner leaflet:
PS & PE, PI,
cholesterol

PS

Phospholipid

PI

PE

Sphingomyelin - SM
Phosphatidylcholine - PC
Phosphatidylserine - PS
Phosphatidylethanolamine - PE
Phosphatidylinositol - PI

Phospholipids
- Account for more than half of the lipid in most membrane;
- Responsible for the basic function of membranes as barriers;
- The long fatty acid chains can move freely in the interior of the
membrane.

phosphotidylinositol

Glycolipids
- Constitute about 2% of the lipids of most plasmas membrane;
- Exclusively in the outer leaflet;
- Its carbohydrate portions exposed on the cell surface play protective
role, as well as involved in cell-cell recognition.

(N-acetylneuraminic Acid)

Cholesterol
- A major constituent of animal cell membrane: about equal molar
amounts as the phospholipids;
- It fills the gap between kinked long fatty acid chains; Help control
membrane fluidity: at high Tm, reduces membrane mobility and permeability;
at low Tm, prevents membrane from freezing.

Synthesis of Phospholipid

- All major lipids of eukaryotic membranes are synthesized by the smooth

ER or Golgi;
- Phospholipids are synthesized from
water soluble cytosolic precursors on
the cytosolic side of the ER memrane;
- New phospholipids are added only to
the cytosolic half of the ER membrane;
- Smooth ER is also the major site for
the synthesis of Cholesterol and
Ceramide. Ceramide is converted to
glycolipids or sphingomyelin.
(Major function of smooth ER: lipid
Metabolism)

How are newly synthesized phospholipids transferred to the lumenal half

of the ER membrane in order to maintain a stable membrane?
- Phospholipid flippase catalyze the
translocation of phospholipids across
the ER membrane resulting in even
growth of both halves of the bilayer;
- Lipids are exported from ER in vesicles
to Golgi, and subsequently to the
plasma membrane.
Inside -out

Inside -in

Membrane Proteins
- Roughly 30% of all animal proteins are membrane proteins.
- Proteins make up from 25-75% of membrane mass with a typical membrane
containing 50% of its mass as protein.

Integral proteins

- Released by membrane disruption

Peripheral and lipid

anchored proteins

- Peripheral proteins are proteins

attached to other membrane proteins
by ionic bonds and can be released
by extreme PH or high salt concentration

Transmembrane proteins
- The transmembrane domains are
usually alpha helices of 20-25
hydrophobic amino acids

Extracellular
domain

Transmembrane
domain

Intracellular
domain

- The transmembrane domains in some cases are beta-sheets. One such

example is the porin family proteins, which form barrel-like channels.

Glycosylation

review

- The process of adding carbohydrates to protein peptides is called glycosylation;

- Glycosylated proteins are called glycoprotein and most ER Proteins Are glycosylated;
- Glycosylation is initiated in ER before translation is completed;
- A common oligosaccharide unit is added to acceptor asparagine residues in the
consensus sequence Asn-X-Ser/Thr by a membrane-bound enzyme called oligosaccharyl
transferase;

Oligosaccharide
unit

Glycocalyx

glycocalyx

- A carbohydrate coat on the outer face of the

plasma membrane, formed by the oligosaccharides of glycolipids and glycoproteins;
- Protects cell surface, also involved in cell-cell
recognition.

cytosol

nucleus

Plasma
membrane

ABO blood type determination by oligosaccharide

groups in glyolipid on red blood cell membrane.

A allele
ABO locus

B allele

Glycosyltransferase)

O allele

Lipid or Glycolipid Attached Proteins

- Covalent bond
- Lipid attached proteins are synthesized on free cytosolic ribosomes
and modified by the addition of lipids;
- Glycosylphosphotidylinositol (GPI) anchored proteins are synthesized
in the ER and transported to the outside of the plasma membrane.

GPI anchored

Lipid anchored

Attachment of Glycolipid

review

Glycolipid (lipid linked to oligosaccharides), also named as glycosyl-phosphotidylinositol

(GPI) due to the presence of phosphatidylinositol, is synthesized inside the ER;
The pre-assembled GPI is added to the carboxy terminus of some proteins that are
retained in the membrane by a C-terminal hydrophobic sequence;
The C-terminal sequence is cleaved and exchanged for the GPI anchor, so the proteins
remain attached to the membrane only by the GPI anchor;
Glycolipid modification helps to attach some proteins to the external face of the PM.

Are membrane proteins mobile?

- protein mobility can be restricted

by membrane protein-protein
interaction, protein interaction with
cytoskeleton, interaction with
extracellular matrix and interaction
with proteins of neighboring cells.

(Larry Frye and Michael Edidin, 1970)

http://www.dnatube.com/video/360/Fluid-Mosaic-Model

Function of Membrane Proteins

- Transporters carry a molecule (such as glucose) from one side of the

plasma membrane to the other.
- Receptors can bind an extracellular molecule (triangle), and this activates an
intracellular process.
- Enzymes in the membrane can do the same thing they do in the cytoplasm
of a cell: transform a molecule into another form.
- Anchor proteins can physically link intracellular structures with extracellular
structures.

Transportation across the plasma membrane

(no external source of energy used)

Passive diffusion
Facilitated Diffusion

- Through the lipid bilayer

- No external energy required
- Concentration gradient dependent

Passive Diffusion

urea

Facilitated Diffusion/Passive Transport

- Concentration gradient dependent (from high to low);
- No external energy required;
- Membrane proteins mediated.

Carrier proteins
-Transport specific molecule by
conformational change

Glucose
Transporters

Channel proteins
- Allow free diffusion of any molecules of
appropriate size and charge through its open
pore

Porins Gap junctions Ion channels

Ligand gated

GLUT1-13

http://sites.sinauer.com/cooper6e/animation0202.html

Voltage gated

Ligand gated

Voltage gated

Presynaptic cell

(-40mV)

Postsynaptic cell

http://sites.sinauer.com/cooper6e/animation1301.html

Active Transport
- Transportation against concentration gradient
ATP hydrolysis driven

Na+-K+ pump

http://sites.sinauer.com/cooper6e/animation1302.html

Ion gradient driven

(energy derived from coupled transport of a

second molecule in the energetically
favorable direction)

Symport
Na+/glucose symporters"
(Apical membrane of intestinal or kidney epithelial cells)

Antiport
Na+/Ca+ antiporters"
Na+/H- exchange protein"

Co-existence of active transport and facilitated diffusion

Endocytosis
- The process of a cell taking up macromolecules and particles from its surrounding medium
Phagocytosis
- Ingestion of large particles such as bacteria

Pinocytosis
- Ingestion of fluids or macromolecules
in small vesicles

pinocytosis

http://sites.sinauer.com/cooper6e/animation1303.html

Endocytosis vs. Exocytosis

http://sites.sinauer.com/cooper6e/video1301.html
http://www.dnatube.com/video/364/Exocytosis-role-of-plasma-membrane

Phagocytosis

Red blood cells

Protist

Amoeba

Macrophage

Human macrophages destroy ~ 1 x 1011 RBC every day

Receptor Mediated Pinocytosis

1500 cholesteryl esters
800 phospholipid

1 apoprotein B100

LDL: low density lipoprotein

Cholesterol uptake

(liver cells, 70% LDL uptake)

http://www.dnatube.com/video/275/How-does-LDL-enter-the-cell
http://www.dnatube.com/video/98/Triskelion-clathrin

LDL receptor pathology: Familial

Hypercholesterolemia

The children were born with blood cholesterol

levels over 1000 mg/dl, and they began
having heart attacks before age 5.

Development of Atherosclerosis: a leading cause of cardiovascular disease

LDL-C: low protein high cholesterol

lipoprotein bad
HDL-C: high protein low cholesterol
lipoprotein - good

http://www.dnatube.com/video/8619/Development-of-atherosclerosis

(Chapter 2 The Composition of Cells p43-p63)

Cellular Composition
Water

Inorganic ions

Organic molecules
Carbohydrates
Lipids

Monosaccharide

Proteins

Fatty acid

Amino acid

Oligosaccharide

Nucleic
Acids

Triacylglycerols
Polypeptide

Polysaccharide

Functions:
Energy storage
Cell structure
Cell recognition and interaction

Phospholipids
Cholesterol
Glycolipids
Energy storage
Membrane structure
Cell signaling

http://sites.sinauer.com/cooper6e/animation0201.html

Nucleotide

Oligonucleotide

Cell structure
Cellular transportation
Cell signaling
Cellular defense
Enzymatic activities

Polynucleotide

DNA

RNA

Genetic information

Carbohydrates
A carbohydrate is a biological molecule consisting of carbon C, hydrogen (H)
and oxygen (O) atoms, usually with a H:O ratio of 2:1 as in water.
Monosaccharides: Glucose, ribose (RNA), deoxyribose (DNA) Galactose
(component of lactose), Fructose (fruit sugar).

Disaccharides: Two joined monosaccharides linked by glycosidic bond. Ex.

Sucrose glucose+fructose (common table sugar);
Lactose galactose + glucose (major sugar in milk);
Maltose - glucose + glucose (product of starch digestion)
2 C6H12O6 H2O = C12H22O11

Oligosaccharides: 3-9 monosaccharides. Part of glycoprotein or glycolipid and serve as

chemical markers (M6P modification for lysosome targeting; ABO blood type specificity etc.)
Polysaccharides: long chains of monosaccharide units bound together by glycosidic
linkages and on hydrolysis (catalyzed by Amylases) give the constituent monosaccharides or
oligosaccharides.
Storage Polysaccharides: Starch & Glycogen (polymers of glucose).
Starch is made up of a mixture of Amylose (linear chain) and Amylopectin (branched
chains). Ex. Rice, potato, wheat and maize.
Animals store excess glucose by polymerizing it to form glycogen, which is structurally
similar to amylopectin. The liver and skeletal muscles are major depots of glycogen.
http://sites.sinauer.com/cooper6e/video0202.html

starch

Structural Polysaccharides: Cellulose (plants) & chitin (crustaceans).

Cellulose is a polymer of glucose bonded by beta-linages which cannot be broken down by
human cells (lack of cellulase). Wood is largely cellulose while cotton and paper are almost
pure cellulose.

Differences between cellulose and starch:

- The orientation of the glycosidic bonds linking the glucose residues are different.
-There are no side chains in cellulose as there are in starch, allowing these linear molecules
to lie close together to form a rigid structure (perfect for plant cell wall).
Chitin is a structural polysaccharide of an amino sugar (N-acetyl glucoseamine). Found in
the wall of hyphae (fungi) and in the exoskeletons of all anthropods (insects and
crustaceans). Beta-1,4 link is broken by chitinase.

http://sites.sinauer.com/cooper6e/video0203.html

Lipids
Include fatty acids, triglycerides (fats), phospholipids; sphingolipid, glycolipid &
steroid lipid (cholesterol and hormones, ex. Estrogen, testosterone, progesterone etc..).
There are 3 essential fatty acids that have to be incorporated in the diet:
linoleic acid, linolenic acid and arachidonic acid.

How does too much of carbohydrates lead to fat accumulation?

Glucose

Acetyl-CoA
Fatty acid
synthase

Lipogenesis

Fatty acid
Triglycerides (fats)
glycerol

Protein

unnatural amino acids

What nutrients are necessary in order to culture animal cells In vitro (outside the
body)?
1. All 20 of the amino acids from which proteins are synthesized;
2. A purine (hypoxanthine) and a pyrimidine (thymidine) for the synthesis of nucleotides
and their polymers, DNA and RNA;
3. 2 precursors (choline and inositol) needed to synthesize some of the phospholipids
in the cell;
4. 8 vitamins, all of which serve as parts of coenzymes;
5. The coenzyme lipoic acid;
6. Glucose as a source of energy and carbon atoms;
7. The inorganic ions: Na+, K+, Ca2+, Cu2+, Zn2+, and Co2+
8. Serum (provides growth factors and hormones for cell survival and division).