Basic Cell Biology

Part II
Biology for
Physical Scientists

Beining Chen, November 2008

1
 Course Objectives

Understanding cellular structure

and functions !!!!

2
 Course Material (1)

Main Reference Book:

Bruce Alberts, Essential Cell
Biology: an introduction to
the molecular biology of the cell,
Garland Publishing,
ISBN: 0-8135-2971-7
Library cat. No.: Q574.87 (E)

Classwire™:
http://www.classwire.com/garlandscience
3
 Course Material (2)

Web CT : PowerPoint slides

Handouts
Quiz
Workshop questions
Group projects
White board
Chat room

http://vista.shef.ac.uk/webct/entryPage.dowebct
Or http://www.sheffield.ac.uk/
Use your CICS username and password. 4
 Course Structure (1)

Part I Membrane Architecture

Part II Transport in and out of cells
Part III Cytoskeletons
Part IV Cell cycles
Part V Extracellular matrix Part VI
Workshop/Tutorial/ Group Project

5
 Course Structure (2)

Assessments:
CHM 1505 Workshop questions – Week 8
CHM6108/DTC Workshop questions + Group
poster/oral presentations on
given topics (Week 8)

Written Examination!!!

6
Introduction

Hierarchy of Biological Systems

100m 1

Organism Unaided eye

Organ system:
>0.1 mm
Digestive

Organs:

Number
Heart, lung

Light microscope
Size

Tissues:
Epithelial, muscular
>0.2 µM
Cells and Organelles:
Cell membrane, Mitochondria

Macromolecules:
Carbohydrate, lipids, proteins & nucleic acids
Electron
Microscope
Molecules and atoms >0.2 nM

0.1 nM Billion
7
What is Cell?
01_03_All from
cells.jpg

8
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What is Cell?
01_01_Cell.shapes.size
s.jpg

10
Cell and its organelles

They all have

membranes!!!

11_03_compartments.jpg

Identify one common

structural element
amongst cells and
their organelles.
11
Part I Membrane Architecture
• Lipid bilayer
• Membrane proteins
• The fluid mosaic model
• Membrane dynamics

12
I. Membrane Functions

11_01_Cell.membranes.jpg

Plasma and internal membrane act as barriers and

separate cells and organelles from their outside world.
13
Membrane Functions

11_02_plasma.membra.jpg

Membranes move, grow, receive

information and allow the exchange
of materials.
14
II. Membrane Structure
All biological membranes are composed of lipids and
Proteins, and share a common generic structure.

11_04_membrane.view.jpg

Membranes are very thin, 5 nm in thickness.

15
III. Membrane Lipid

Lipid composition of membranes

1. Phospholipids
1. Glycerophospholopids
Phosphatidylcholine(PC)
Phosphatidylethanolamine(PE)
Phosphatidylserine (PS)
2. Sphingolipids
2. Cholesterol
3. Glycolipids

16
11_07_amphipathic.jpg

17
All lipid molecules are amiphipathic, i.e
containing both hydrophilic and hydrophobic
Functional groups.

11_05_tails.philic.pho.jpg

18
Lipids are different from fats

Fat Lipid

Lipids have
charged hydrophilic
heads instead of
hydrophobic tails.

19
1. Phospholipids (glycerophospholipds)

11_06_Phosphatidylch.jpg

Glycerophospholipids are composed of 4 parts:

charged base, phosphate, glycerol, and 2 hydrocarbon tails.
Different bases and tails make different lipids. 20
Common glycerophospholipids

Phosphatidylcholine (PC)

Phosphatidylethanolamine (PE)

Phosphatidylserine (PS)

21
Hydrocarbon tails - fatty Acids

Phosphatidylcholine (PC), Lecithins

R1 = palmitic acid C16H32O2 or

stearic acid C18H36O2. They are
straight chains

R2 = oleic acid C18H34O2

or linoleic acid C18H32O2.They
contain double bonds and are
bend. 22
Sphingolipids
- Instead of a glycerol backbone it contains
sphingosine, an amino alcohol with a long
unsaturated hydrocarbon chain.

Sphingomyelin

R2-hydrocarbon
chain

23
2. Cholesterol

11_16_Cholesterol.jpg

It is a steroid and an important membrane component.

It fits into the gaps between phospholipids molecules in a
lipid bilayer.
24
3. Glycolipids

Sphingolipids

All phospholipids can be glycated. Glycolipids

always sit on the outer leaflet of Membrane.

25
 4. Amphipathic Phospholipids form bilayer

Experimental evidence 1 – synthetic lipids

Pure phospholipids can form a closed, spherical bilayer liposome.

26
Experimental evidence 1 – synthetic lipids

11_14_synth.phospho.jpg

Pure phospholipids can form flat bilayer across a hole

in a partition between 2 aqueous compartments.
27
 Experimental evidence 2 – Freeze fracture

Homogeneous regions - lipid

leaflet; bumps – proteins.

The two fractured sections are coated with heavy metal

(etched) and a replica is made of their surfaces.
28
5. Lipid composition various in different membranes

29
6. Membrane lipids are asymmetrical

11_17_asymmetic.dist.jpg

30
Phospholipids Distribution

31
7. Lipid bilayer spontaneously close in on
themselves to form sealed compartment.

32
Which of the following membrane lipids does
not contain a fatty acid tail?
(a) Phosphatidylcholine
(b) A glycolipid
(c) Phosphatidylserine
(d) Sphingomyelin
(e) Cholesterol

33
Which of the following membrane lipids does
not contain a fatty acid tail?
(a) Phosphatidylcholine
(b) A glycolipid
(c) Phosphatidylserine
(d) Sphingomyelin
(e) Cholesterol

34
Membrane Proteins

11_20_memb.proteins.jpg

Membrane proteins act as transporters, anchors,

Receptors and enzymes

35
Integral or intrinsic Proteins (A)

11_21_proteins.associ.jpg

Peripheral or extrinsic Proteins (B, C, D)

36
Peripheral & integral
membrane proteins
Some peripheral proteins are attached to the
membrane by electrostatic attraction with the
charged lipid heads; e.g. cytochrome c is positively
charged and interacts with negatively charged
lipids. They can be removed by gentle methods.

Integral proteins have hydrophobic areas inside

membrane, whereas hydrophilic parts stick out into
the cytoplasm, e.g. cytochrome oxidase. They can be
removed by detergents.

37
Disruption of the
membrane protein

11_27_Triton X-100.jpg

38
11_28_Bacteriorhodop.jpg

39
Which of the following statements regarding membrane
proteins is FALSE?
(a) Integral membrane proteins often precipitate
(form insoluble aggregates) in aqueous solutions
lacking detergents.
(b) Some hydrophobic amino acids in membrane proteins
are not in contact with the lipid bilayer.
(c) Peripheral membrane proteins can be dissociated
from membranes using a gentle detergent.
(d) Strong detergents can completely unfold both
membrane and nonmembrane proteins.
(e) In transmembrane proteins that form an aqueous
pore through the membrane, the pore is lined with
hydrophobic amino acid side chains.

40
Which of the following statements regarding membrane
proteins is FALSE?
(a) Integral membrane proteins often precipitate
(form insoluble aggregates) in aqueous solutions
lacking detergents.
(b) Some hydrophobic amino acids in membrane proteins
are not in contact with the lipid bilayer.
(c) Peripheral membrane proteins can be dissociated
from membranes using a gentle detergent.
(d) Strong detergents can completely unfold both
membrane and nonmembrane proteins.
(e) In transmembrane proteins that form an aqueous
pore through the membrane, the pore is lined with
hydrophobic amino acid side chains.

41
V. Dynamic Nature of Membranes
1. Fluid-mosaic model
The membrane is composed of a number of proteins
which are similar to shifting tiles. The spaces
between the tiles are filled with fluid-like
phospholipids. Both lipids and membrane proteins are
constrained within the plane of the membrane, but
are free to diffuse laterally.

42
Lipid Mobility
Lateral diffusion
Flexion
Rotation
Flip-flop (rare)

11_15_Phospho,move.jpg

The degree of fluidity depends on the nature of fatty

tails. The more saturated, the less fluidic.
43
 The role of flippases

11_18_Flippases.jpg
Flappases
transfer some of
these to the
opposite side of
the membrane so
that the entire
bilayer expands.

44
Membrane fluidity
Experiment 1 – Fluorescence (labelled antibodies)

11_34_hybrid cells.jpg

At lower temperatures, process is slower because

of decreased fluidity.
45
Experiment 2 -Fluorescence Recovery After Photobleaching

11_36_FRAP.jpg

46
Which of the following statements regarding lipid
membranes is TRUE?
(a) Phospholipids will spontaneously form liposomes
in nonpolar solvents.
(b) In eucaryotes, all membrane-enclosed organelles
are surrounded by one lipid bilayer.
(c) Membrane lipids diffuse within the plane of the
membrane.
(d) Membrane lipids frequently flip-flop between one
monolayer and the other.
(e) The preferred form of a lipid bilayer in water is
a flat sheet with exposed edges.

47
Which of the following statements regarding lipid
membranes is TRUE?
(a) Phospholipids will spontaneously form liposomes
in nonpolar solvents.
(b) In eucaryotes, all membrane-enclosed organelles
are surrounded by one lipid bilayer.
(c) Membrane lipids diffuse within the plane of the
membrane.
(d) Membrane lipids frequently flip-flop between one
monolayer and the other.
(e) The preferred form of a lipid bilayer in water is
a flat sheet with exposed edges.

48
A bacterium is suddenly expelled from a warm human
intestine into the cold world outside. Which of the
following adjustments might the bacterium make to
maintain the same level of membrane fluidity?
(a) Increase the length of the hydrocarbon tails in
its membrane phospholipids.
(b) Increase the proportion of unsaturated
hydrocarbon tails in its membrane phospholipids.
(c) Increase the proportion of hydrocarbon tails with
no double bonds in its membrane phospholipids.
(d) Decrease the amount of cholesterol in the
membrane.
(e) Decrease the amount of glycolipids in the
membrane.

49
A bacterium is suddenly expelled from a warm human
intestine into the cold world outside. Which of the
following adjustments might the bacterium make to
maintain the same level of membrane fluidity?
(a) Increase the length of the hydrocarbon tails in
its membrane phospholipids.
(b) Increase the proportion of unsaturated
hydrocarbon tails in its membrane phospholipids.
(c) Increase the proportion of hydrocarbon tails with
no double bonds in its membrane phospholipids.
(d) Decrease the amount of cholesterol in the
membrane.
(e) Decrease the amount of glycolipids in the
membrane.

50
Summary
1.Cells are basic building blocks of life;
2.Cells vary enormously in appearance and function;
3.Cells Grow, reproduce, use energy, adapt, respond to their
environment;
4.Cells have a similar basic chemistry;
5.Macromolecules (proteins, DNAs, lipids and polysaccharides)
assemble into different parts of the cell via covalent bonds
and non-covalent forces;
6.Biological membranes are bilayers composed of lipids and
proteins;
7.Biology membranes are barriers to water-soluble molecules
and thus form intercellular and intracellular compartments;
8.In addition to acting as a barrier, the plasma membrane must
act as a mediator because it forms the interface between the
cell and the environment;
9.Membranes are dynamic in nature and membrane fluidity is
crucial for its functions.

Further Reading: Essential Biology, Chapter 11 51