CELL MEBRANE &

EXTRACELLULAR MATRIX
1,2
Marhaen Hardjo
1
Head of Biochemistry Department, Medical Faculty of Hasanuddin University
2
Director of Stem Cell Center Hasanuddin University Hospital

DEPARTMENT OF
BIOCHEMISTRY MEDICAL
FACULTI OF HASANUDDIN
UNIVERSITY
AP Biology
 The Cell Membrane

AP Biology 2007-2008
 Overview
 Cell membrane separates living cell from
nonliving surroundings
 thin barrier = 8nm thick
 Controls traffic in & out of the cell
 selectively permeable
 allows some substances to cross more easily
than others
 hydrophobic vs hydrophilic

 Made of phospholipids, proteins & other

macromolecules

AP Biology
 Phosphate
Phospholipids
 Fatty acid tails
 hydrophobic
 Phosphate group head
Fatty acid
 hydrophilic
 Arranged as a bilayer

Aaaah,
one of those
structure–function
examples
AP Biology
 Phospholipid bilayer

polar
hydrophilic
heads

nonpolar
hydrophobic
tails

polar
hydrophilic
heads

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 More than lipids…
 In 1972, S.J. Singer & G. Nicolson
proposed that membrane proteins are
inserted into the phospholipid bilayer

It’s like a fluid…

It’s like a mosaic…
It’s the
Fluid Mosaic Model!

AP Biology
Membrane is a collage of proteins & other molecules
embedded in the fluid matrix of the lipid bilayer

Glycoprotein Extracellular fluid

Glycolipid

Phospholipids
Cholesterol
Transmembrane
proteins
Peripheral
protein
Cytoplasm Filaments of
cytoskeleton
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 Membrane fat composition varies
 Fat composition affects flexibility
 membrane must be fluid & flexible
 about as fluid as thick salad oil
 % unsaturated fatty acids in phospholipids
 keep membrane less viscous
 cold-adapted organisms, like winter wheat
 increase % in autumn
 cholesterol in membrane

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 Membrane Proteins
 Proteins determine membrane’s specific functions
 cell membrane & organelle membranes each have
unique collections of proteins
 Membrane proteins:
 peripheral proteins
 loosely bound to surface of membrane
 cell surface identity marker (antigens)
 integral proteins
 penetrate lipid bilayer, usually across whole membrane
 transmembrane protein
 transport proteins
 channels, permeases (pumps)
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 Why are
proteins the perfect
molecule to build structures
in the cell membrane?

AP Biology 2007-2008
 Classes of amino acids
What do these amino acids have in common?

nonpolar & hydrophobic

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 Classes of amino acids
What do these amino acids have in common?

I like the
polar ones
the best!

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polar & hydrophilic
 Proteins domains anchor molecule
Polar areas
 Within membrane of protein
 nonpolar amino acids
 hydrophobic
 anchors protein
into membrane
 On outer surfaces of
membrane
 polar amino acids
 hydrophilic
 extend into
extracellular fluid &
Nonpolar areas of protein
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into cytosol
 H+

Examples Retinal
chromophore
NH2

water channel
in bacteria
Porin monomer
-pleated sheets

Bacterial Nonpolar
outer (hydrophobic) COOH
membrane -helices in the
cell membrane H+
Cytoplasm

proton pump channel

in photosynthetic bacteria
function through
conformational change =
AP Biology shape change
 Many Functions of Membrane Proteins
Outside

Plasma
membrane

Inside
Transporter Enzyme Cell surface
activity receptor

Cell surface Cell adhesion Attachment to the

AP Biology identity marker cytoskeleton
 Membrane carbohydrates
 Play a key role in cell-cell recognition
 ability of a cell to distinguish one cell
from another
 antigens
 important in organ &
tissue development
 basis for rejection of

foreign cells by
immune system

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 Any Questions??

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 Movement across the
Cell Membrane

AP Biology 2007-2008
 Diffusion
 2nd Law of Thermodynamics
governs biological systems
 universe tends towards disorder (entropy)

 Diffusion
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 movement from high  low concentration
 Diffusion
 Move from HIGH to LOW concentration
 “passive transport”
 no energy needed
movement of water

AP Biology diffusion osmosis

 Diffusion across cell membrane
 Cell membrane is the boundary between
inside & outside…
 separates cell from its environment
Can it be an impenetrable boundary? NO!

IN OUT
food waste
carbohydrates OUT ammonia
sugars, proteins salts
amino acids CO2
IN
lipids H2O
salts, O2, H2O products
AP Biology
cell needs materials in & products or waste out
 Diffusion through phospholipid bilayer
 What molecules can get through directly?
 fats & other lipids

lipid
 What molecules can
inside cell NOT get through
NH3 salt directly?
 polar molecules
 H 2O
 ions
 salts, ammonia
sugar aa H 2O
outside cell  large molecules
 starches, proteins
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 Channels through cell membrane
 Membrane becomes semi-permeable
with protein channels
 specific channels allow specific material
across cell membrane

inside cell H 2O aa sugar

NH
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3
salt outside cell
 Facilitated Diffusion
 Diffusion through protein channels
 channels move specific molecules across
cell membrane
facilitated = with help
 no energy needed
open channel = fast transport
high

low
AP Biology “The Bouncer”
 Active Transport
 Cells may need to move molecules against
concentration gradient
 shape change transports solute from
one side of membrane to other
 protein “pump”
conformational change
 “costs” energy = ATP low

ATP

high
AP Biology “The Doorman”
 Active transport
 Many models & mechanisms

ATP ATP

antiport symport
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 Getting through cell membrane
 Passive Transport
 Simple diffusion
 diffusion of nonpolar, hydrophobic molecules
 lipids
 high  low concentration gradient
 Facilitated transport
 diffusion of polar, hydrophilic molecules
 through a protein channel
 high  low concentration gradient
 Active transport
 diffusion against concentration gradient
 low  high
 uses a protein pump ATP
 requires ATP
AP Biology
 Transport summary
simple
diffusion

facilitated
diffusion

active ATP
transport
AP Biology
 How about large molecules?
 Moving large molecules into & out of cell
 through vesicles & vacuoles
 endocytosis

 phagocytosis = “cellular eating”

 pinocytosis = “cellular drinking”
 exocytosis

AP Biology exocytosis
 Endocytosis
fuse with
phagocytosis lysosome for
digestion

pinocytosis non-specific
process

triggered by
receptor-mediated molecular
endocytosis signal
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 The Special Case of Water

Movement of water across

the cell membrane

AP Biology 2007-2008
 Osmosis is diffusion of water
 Water is very important to life,
so we talk about water separately
 Diffusion of water from
high concentration of water to
low concentration of water
 across a
semi-permeable
membrane

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 Concentration of water
 Direction of osmosis is determined by
comparing total solute concentrations
 Hypertonic - more solute, less water
 Hypotonic - less solute, more water
 Isotonic - equal solute, equal water

water

hypotonic hypertonic
AP Biology net movement of water
 Managing water balance
 Cell survival depends on balancing
water uptake & loss

AP Biology freshwater balanced saltwater

 Managing water balance
 Isotonic
 animal cell immersed in
mild salt solution
 example:
blood cells in blood plasma
 problem: none
 no net movement of water
 flows across membrane
equally, in both directions
 volume of cell is stable

AP Biology balanced
 Managing water balance
 Hypotonic
 a cell in fresh water
 example: Paramecium
 problem: gains water,
swells & can burst
 water continually enters
Paramecium cell
 solution: contractile vacuole
ATP  pumps water out of cell
 ATP
 plant cells
 turgid
AP Biology freshwater
 Water regulation
 Contractile vacuole in Paramecium

ATP

AP Biology
 Managing water balance
 Hypertonic
 a cell in salt water
 example: shellfish
 problem: lose water & die
 solution: take up water or
pump out salt
 plant cells
 plasmolysis = wilt

AP Biology saltwater
 1991 | 2003
Aquaporins
 Water moves rapidly into & out of cells
 evidence that there were water channels

Peter Agre Roderick MacKinnon

John Hopkins Rockefeller
AP Biology
 Osmosis…

.05 M .03 M

Cell (compared to beaker)  hypertonic or hypotonic

Beaker (compared to cell)  hypertonic or hypotonic
Which way does the water flow?  in or out of cell
AP Biology
 Any Questions??

AP Biology
 EXTRACELLULAR MATRIX/ADHESION

Reading:
Molecular Biology of the Cell Chapter 19 is
required reading, except for information pertaining to
nonmammalian cells, and to embryology.

The lecture is based on this chapter, but will only

cover a portion of the required material, plus
additional information not included in the text.

The extracellular matrix and cellular adhesive

events have fundamental roles in embryonic
development. Time and effort considerations result
in the exclusion of this area.
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 Fig. 19-1 Simplified drawing of a cross-section through
part of the wall of the intestine. Each tissue is an organized
assembly of cells held together by cell-cell adhesions, extracellular
AP Biology
matrix, or both.
 CELL-CELL ADHESION

Largely self-study:
 types of cell-cell adhesive interactions
[junctional: occluding (tight), adherens,
desmosomes & gap; +
nonjunctional]
 constituents (plasma membrane and
cytoskeletal, if any) and structures
of each type of cell-cell interaction
 functional roles of each type of cell-cell
adhesion
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 A Summary of Junctional and
Nonjunctional Adhesion

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Fig. 19-28
Cell-Cell Adhesion: Major
Plasma Membrane Proteins
Junction Protein family

Tight Occludins & claudins (not in text)

Adhesion Cadherins, e.g., E-cadherin
Desmosome Cadherins
Gap Connexins
nonjunct. Ig-like, e.g., N-CAM
nonjunct. Selectins*, e.g., E-selectin
nonjunct. Integrins*
* cell-cell adhesion in a limited number of cell types
AP Biology
 Functions of Tight
Junctions
 Restricts movement
of plasma membrane
proteins & lipids
between the apical
and basolateral
membranes

 Barrier to diffusion of
molecules across the
epithelial cell sheet

AP Biology
Fig. 19-3A
 EXTRACELLULAR MATRIX
(ECM)
 Extracellular
network of
macromolecule
s

 Components
secreted
locally;
organized by
cells associated
with the matrix
AP Biology
Fig. 19-31
 BASAL LAMINA

 Flexible, thin mat

of specialized
ECM
 Often termed
basement
membrane
 In close
association with
cells, as
illustrated at
right, Fig.19-53.
AP Biology
 MAJOR ECM CONSTITUENTS

 Hyaluronan
 Proteoglycans
 Collagens
 Elastin
 Fibronectin
 Laminin
 Enactin/
nidogen
Fig. 19-57 Protein in green,
AP Biology
glycosaminoglycan in red.
Plasma Membrane Constituents
which Bind to the ECM
 Integrins
 Proteoglycans

AP Biology Fig. 19-28

 INTEGRINS

 Plasma membrane
heterodimers
 Have ECM or
surface membrane
binding domain(s)
 Have divalent
cation binding sites
 Many participate in
linking the ECM to
the cytoskeleton

AP Biology
Fig. 19-60
AP Biology Circ Res 89:211. 2001
Integrins and
their
ligands

J Biol Chem
275:21785,
2000

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 J Biol Chem 275:21785, ‘00
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 PLASMA MEMBRANE
PROTEOGLYCANS

AP Biology
Annu Rev Biochem 68:729,’99
 HYALURONAN

Fig. 19-35
Disaccharide structure

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Fig. 19-34 Relative volumes
Table 19-3 Some Common Proteoglycans

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 COLLAGENS

 A helix comprised of
homotrimer & heterotrimer
polypeptides (alpha chains)
 Major proteins of ECMs
 Many different alpha chains
 Multiple structures (involves
cross-linking of chains)
 fibrils

 network forming

 fibril-associated

AP Biology Fig. 19-40

Table 19-4 Some types of collagen & their
properties

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 Formation of Collagen
FIBRILS and FIBERS

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Fig. 19-43
Formation of Collagen Networks

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Fig. 19-52
 COLLAGEN ASSEMBLIES

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ELASTIC FIBERS
 Elastin, main constituent
 Fibers crosslinked to form a network
 Fibers & network can extend and recoil

Fig. 19-50
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MICROFIBRILS

 Cover elastin core of elastic fibers

 Also found in other extracellular
matrices
 Contain glycoproteins including fibrillin

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 FIBRONECTIN (FN)
 Extracellular dimeric
glycoprotein
 Differential splicing
 Multiple functional
domains
 cell binding
 RGD sequence of FN
 other specificities
 heparin binding
 collagen binding
 fibrin binding
 Organized into a matrix
AP Biology
Fig. 19-51 A,C
LAMININ

 Heterotrimeric glycoprotein
 Basal lamina constituent
 Multiple binding domains

AP Biology Fig. 19-55

 Binding Domains of Laminin

 Self assembly
 Type IV collagen
 Heparan sulfate
 Enactin/nidogen
 Cell Surface
 integrin
 nonintegrin

Cell Suface Binding Sites

AP Biology J. Anat. 193:1, ‘98
 BASAL
AP Biology
LAMINA
Fig. 19-56
 HEMIDESMOSOMES

 Junctions linking the

intermediate filaments
to the ECM
 Constituents include
 integrins
 other plasma
membrane proteins
 cytosolic proteins
 Functions include
 adhesion
 intracellular signaling
AP Biology
Bioessays 20:488, ‘98
 Focal Adhesion (Focal Contact or
Adhesion Plaque)
 Junctions linking actin
filaments to the ECM
 Constituents include
 integrins
 cytosolic proteins
 Functions include
 adhesion
 cell signaling

AP Biology
Fig. 16-75B
 INTEGIN-ECM SIGNALING

Curr Opin Cell Biol 11:634, ‘99

“inside-out” signals (1-3)
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Biochem J 339:481, ‘99
Diversity in Adhesive Interactions

 Diversity in the major components due to:

 differential splicing
 post-translational modifications

 different gene products

 Participation of additional molecules

AP Biology
 Matrix Metalloproteases
 Also termed matrix metalloproteinases,
matrixins, MMPs
 Enzymes which cleave ECM
constituents, including
collagenases
 Contain a propeptide which must be
cleaved for enzyme activity
 Multiple mechanisms to regulate MMP
activity, including inhibition by tissue
inhibitors of metalloproteases (TIMPs)
 Other functional domains
AP Biology
 Matrix Metalloproteases

AP Biology
Genes Dev 14:2123,’00
AP Biology
Genes Dev 14:2123,’00
ADAM
A Disintegrin And Metalloprotease

T=
transmembrane
domain

A disintegrin is a molecule that binds to an integrin.

AP Biology
Trends Genet. 16:83, ‘00
AP Biology
Trends Genet. 16:83, ‘00