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Theory, Concepts & Models
PLASMA MEMBRANE
Rohit Mondal
B.Sc (Life Science) 3rd yr
Roll no.- 7030 /16
DSE-Cell and Molecular biology
Content :-
 Definition of Membrane and
Plasma membrane
 Structure of membrane
 Some general properties of
Plasma membrane
 Chemical composition of
memb.
 History of Plasma
Membrane
 Establishment of the Idea of
a Cell Barrier
 Different Models related to
Plasma membrane :-
 Overton’s model of
Plasma membrane
 Phospholipid bilayer
model
 Sandwich Model
 Unit membrane model
 Fluid mosaic model
 Modified Fluid mosaic
model
 Lipid raft model*
 Conclusion
* *
What is a membrane?
 A thin sheet of tissue or layer of cells acting as a
boundary, lining, or partition in an organism.
What Is a Plasma Membrane?
 An outermost envelope surrounding the cell that
separates and protects the cell from the external
environment and provides a connecting system B/w
the cell and its environment is called plasma
membrane.
 It appears in thin sections with the electron
microscope as a triple-layered structure about 7.5–10
nanometers thick.
 Term coined by C. Nageli and C. Cramer in 1855,
and Plasmalemma coined by J. Q. Plowe in 1931.
Membrane Structure
 Membranes consist of a phospholipid bilayer
combined with a variety of proteins in a fluid mosaic
arrangement .
 The surfaces of cell membranes are hydrophilic
(water-loving); the interiors are hydrophobic
Some general properties of Plasma
Membrane
 Keeps a cell intact.
 Protective barrier.
 Regulate transport in & out of cell (selectively
permeable).
 Small lipid-soluble molecules, e.g. oxygen and
carbon dioxide can pass easily .
 Water can freely cross the membrane.
 Ions and large molecules cannot cross without
assistance .
 Allow cell recognition & provide anchoring sites for
filaments of cytoskeleton.
 Provide a binding site for enzymes.
Chemical Composition of Plasma
Membrane
 Lipids -four major classes of lipids are commonly
present in the plasma membrane: phospholipids (most
abundant), spingolipids, glycolipids and sterols (e.g.
cholesterol). All of them are amphipathic. Cholesterol is
abundant in mammalian cell and is absent in
prokaryotic cells.
 Proteins -plasma membrane contains about 50%
protein. Amount and type is variable. Myelin cells
contains about 25% protein internal membranes of
chloroplast and mitochondria contains 50% protein.
Proteins of plasma membranes are of two types
ectoproteins and endoproteins. Plasma membranes
contains structural proteins, transport proteins and
enzymes. Some of them acts as receptors. (enzymes
present in the plasma membrane are Acetyl
phosphatase, acid phosphatase, ATPase, RNAase,
 Carbohydrates- they are present only in the
plasma membrane and are present exterior
(glycoproteins) or polar end of phospholipids at
the external surface of plasma membrane.
History of the Plasma Membrane
1895: Charles Overton - Composed of lipids
1925: E. Gorter and G. Grendel - Phospholipid bilayer
1935: J.R. Danielli and H. Davson - Proteins also part,
proposed the Sandwich Model
1950’s: J.D. Robertson - Proposed the Unit Membrane
Model
1972: S.J. Singer and G.L. Nicolson – Proposed Fluid
Mosaic Model
Establishment of the Idea of a Cell
Barrier
 17th century: Invention of microscopes enabled
closer examination of various tissues. Upon looking
at the tissues under a lens, scientists discovered
small, room-like spaces that they gave the name
"cells," with barriers between each space. Similar
barriers were assumed to exist in animal cells,
though they could not be seen.
Overton’s model of Plasma
Membrane
 Overton develops concept of a lipid membrane and
according to him a lipid bilayer consists of two
apposed lipid monolayers with the hydrophilic lipid
head groups facing the surrounding fluid spaces on
each side of the bilayer and the hydrophobic lipid
hydrocarbon chains localized in the bilayer center.
Such an arrangement of lipid molecules represents
an ideal functional and structural boundary for cells.
The ion gradients across membranes, produced by
membrane-embedded ion pumps, are critical to cell
functions, including the production of ATP, nerve
conduction, and muscle contraction.
N
N
N
Phospholipid bilayer model
(Gorter & Grendel’s work)
 In 1925, Gorter and Grendel, stimulated by the findings of
Franklin and Overton, performed a series of studies that
had a major impact on all subsequent thinking dealing
with membrane structure.
 These investigators extracted the lipids from erythrocyte
membranes of a variety of species and and then
spreading the lipids as a mono-layer in a Langmuir-
Blodgett trough and then calculated the area covered by
these lipids when spread on water to form a
monomolecular layer.
 They also approximated the total area of the membranes from
which the lipid was extracted and concluded that the area of
the monomolecular layer was twice the membrane area; that
is, there was sufficient lipid to form a double or bimolecular
layer of lipid around the cells, with each layer being about 25 A
thick.
 Oil spreads at air–water interfaces. a Oil molecules spontaneously
spread on the air–water interface until they form a layer one
molecule thick. b Langmuir trough allows to precisely measure the
surface that these monolayers can spread depending on the applied
pressure
Based on their observation of their expt. which
they did. They hypothesized :-
 Cell membranes are made of two opposing thin lipid
double layers
 Polar head groups pointing toward the aqueous
environment (Polar heads face out and Nonpolar tails
face in)
Surface measurement of membrane lipid monolayers as a way to determine membrane
structure. Summary of the method, consisting in the comparison between the area of
lipidsextracted from erythrocyte membranes and the estimated surface area of cells.
The ratio of 2:1indicated the lipid bilayer structure
Sandwich Model
(Danielli & Davson Model)
 In 1935, Davson and Danielli modified the model
proposed by Gorter and Grendel by including protein
in the membrane structure.
 As because the model provided by Gorter & Grendel
could not account for the manifold of functions
attributed to cell membranes. (Does not explain why
some nonlipids are permeable) and their model could
not provide answers to questions on surface tension,
permeability, and the electric resistance of
membranes.
 Therefore, physiologist H. Davson & biologist J.
Danielli suggested that membranes indeed do have
proteins. According to them, the existence of these
"membrane proteins" explained that which couldn't be
 Therefore, in 1935 Danielli and Davson proposed a
sandwich membrane model (the Davson–Danielli
model or the protein–lipid–protein model) in this
model, the lipid layer was covered by a thin protein
layer on both sides. This observation was significant
progress in understanding better the compositional
nature of biological membranes.
 The Davson-Danielli model immediately became
popular, and it dominated cell membrane studies for
the following 30 years. There were some light
polarization and X-ray diffraction studies to support
the model.
 In summary, the Davson-Danielli model took into
account the difference between the physical
properties measured for natural membranes and
membranes composed of pure lipids, for example,
the low values of surface tension measured in the
1920s and 1930s in plasma membranes compared
to lipid bilayers.
 However, although the researchers were conscious
of the permeability of ions, sugars, and other
hydrophilic solutes, the model they postulated
implied that the protein layer did not interact with the
hydrophobic parts of the lipid bilayer and that the
protein layer formed by simple physical adsorption.
 lk
Unit Membrane model of Plasma
Membrane
 In 1959, Robertson compared a collection of cross-
section pictures and observed that the whole railroad
track was consistent in a variety of cells
 He thought that the railroad track fit the Davson–
Danielli model and extended it as the unit membrane
or the Davson– Danielli–Robertson (DDR) model.
 Robertson stressed two points in the model: first, that
the three layers observed in the electron microscope
cross-section shots were part of the same structure,
the cell membrane, regardless of the other cell
envelopes that might exist; and second, that this
structure was universally shared among all biological
membranes
 The unit membrane model assigned the bilayer
structure to all membrane systems, including cell
membranes and cellular organelle membranes
Unit membrane concept. Railroad track images from thin
section electron microscopy of osmium-fixed cells: two dark
lines separated by a clear region. Robertson summarized the
available data and used many new examples to make the point
that all cell membranes have a common structure..
 nn
Unit Membrane model of Plasma
membrane
Fluid Mosaic Model of Plasma
memb. With the development of the freeze-fracture technique and
immuno-electron microscopy, researchers identified
antibody-recognizing isolated membrane proteins and
proteins that spanned the lipid bilayer.
 In 1972, Singer and Nicolson proposed their celebrated
fluid mosaic model (FMM) of biological membranes and
this model has since been a central paradigm in
membrane science.
 The basics of the model have remained the same ever
since the membrane is a lipid bilayer with hydrophilic parts
on the sides and hydrophobic parts in the interior; proteins
can interact with surface through transient polar contacts,
but a lot of proteins are partially or totally embedded in the
lipid bilayer where their hydrophobic parts also interact
 Considering the big controversy going on at the
beginning of the 1970s, the FMM incorporated for
the first time many relevant experimental facts
and the development of techniques:-
I. The permeability and transport studies that
predicted enzyme-like transmembrane proteins.
II. The apparent lack and limited transverse mobility
of lipids to make up complete bilayers , thus
pointing out to the participation of proteins in the
membrane plane.
III. Electron microscopy pictures,including freeze-
etching technique and immuno-EM studies that
identified antibody -recognizing isolated membrane
proteins.
IV. The stability of artificial lipid bilayers that
Salient feature of Fluid mosaic
model
 The specific features and important contributions
of the model are demonstrated in detail as
follows.
 the model recovered the lipid bilayer concept from
Danielli and Davson as mentioned above. Membrane
lipids are amphipathic. They possess both a hydrophobic
and a hydrophilic moiety. Because of this amphipathic
character, in an aqueous medium they can organize
themselves on both sides of an imaginary plane, with the
hydrophobic portions facing each other, and the polar
moieties oriented to the outer, aqueous space.
 membrane proteins can be associated either to the lipid
 both lipids and proteins are in constant motion. In
principle, three main of motion could be considered,
rotational, translational, and transbilayer.
 the asymmetry of membranes has also proven to be
a fruitful characteristic.
Fluid mosaic model
 k
Fluid mosaic model
Modified Fluid Mosaic Model
 In 2005, Engelman proposed an update of the
Singer–Nicolson model . He put forward the idea that
“membranes are more mosaic than fluid.”
Transmembrane proteins are so frequent in
membranes that hardly any lipid molecule in the
bilayer is left unperturbed.
An amended and
updated version of the
fluid mosaic model with
more mosaic proteins.
 Apart from the high density of transbilayer proteins in the
membrane, he also pointed out three other features that
are now considered to occur in most cell membranes. :-
I. Integral proteins exist voluminous extramembrane domains.
This conclusion has been proved by the increasing data of
the three-dimensional structures of many membrane
proteins.
II. Contacts between proteins are more frequent. This
phenomenon is observed in multiple events, for example, G-
protein-mediated signaling, in which a receptor protein will
physically interact with a G-protein that, in turn, will
transiently bind and activate a cyclic ATPase, thus triggering
a cellular response to the signal.
III. The thickness of the lipid bilayer is uneven. Because the
transmembrane portions of intrinsic membrane proteins
exhibit a rough surface, and the whole domains have a
 This updated model incorporates recent information
on both membrane proteins and lipids, containing
membrane domains, lipid rafts, and cytoskeletal
fencing that were unknown in the 1970s.
Schematic illustration of a modification of the fluid mosaic membrane model. Different
lipids are indicated in various colors forming specialized domains around integral
membrane proteins and glycoproteins as well as being asymmetrically distributed across
the membrane.
Lipid raft model of Plasma
memb.* Simons and Ikonen in 1997 postulated particular
functional aspects of specialized domains called lipid rafts
in biological membranes.
 The lipid raft hypothesis proposes that the lipid bilayer is
not a structurally passive solvent, but that the preferential
association between sphingolipids, sterols, and specific
proteins bestows cell membranes with lateral segregation
potential.
 The lipid raft model has long suffered controversy since
there is little direct quantitative experimental evidence
that such domains exist. The traditional method to study
lipid rafts and their association with certain membrane
proteins is based on the observation of the detergent-
resistant membranes (DRMs), composed of mainly
sphingomyelin, other saturated phospholipids,
Controversies of Lipid raft model
 The lipid raft model has long suffered controversy since there
is little direct quantitative experimental evidence that such
domains exist. The traditional method to study lipid rafts and
their association with certain membrane proteins is based on
the observation of the detergent-resistant membranes
(DRMs), composed of mainly sphingomyelin, other sat.
phospholipids, cholesterol, and GPI-anchored proteins
 This tech. was severely criticized, because it
utilizeddetergents that might induce phase separation and/or
affect the partitioning.
Strengths and weaknesses of the most common methods for
characterization of lipid rafts.
Conclusion
 With the development of various techniques, our
understanding of the structure and function of the cell
membranes is more thorough and comprehensive.
 Another fact of note is that every achievement made in the
field of the cell membrane depends on the development of
new techniques and experimental approaches. From
traditional methods such as electron microscopy, X-ray
crystallograph, fluorescence microscopy, nuclear magnetic
resonance spectroscopy, and mass spectroscopy, to modern
methods like atomic force microscopy (AFM) all the
techniques have provided and will provide the significant
information of the membrane structure.
 Moreover, we should know that one model cannot fit
every cellular membrane under all conditions. Therefore,
the cell membrane structure needs to be refined and
modified continually and considered on each specific
case, such as different cell types and external
environments.
THANK YOU

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Plasma membrane - The Nature protection from the outside world

  • 1. Theory, Concepts & Models PLASMA MEMBRANE Rohit Mondal B.Sc (Life Science) 3rd yr Roll no.- 7030 /16 DSE-Cell and Molecular biology
  • 2. Content :-  Definition of Membrane and Plasma membrane  Structure of membrane  Some general properties of Plasma membrane  Chemical composition of memb.  History of Plasma Membrane  Establishment of the Idea of a Cell Barrier  Different Models related to Plasma membrane :-  Overton’s model of Plasma membrane  Phospholipid bilayer model  Sandwich Model  Unit membrane model  Fluid mosaic model  Modified Fluid mosaic model  Lipid raft model*  Conclusion * *
  • 3. What is a membrane?  A thin sheet of tissue or layer of cells acting as a boundary, lining, or partition in an organism. What Is a Plasma Membrane?  An outermost envelope surrounding the cell that separates and protects the cell from the external environment and provides a connecting system B/w the cell and its environment is called plasma membrane.  It appears in thin sections with the electron microscope as a triple-layered structure about 7.5–10 nanometers thick.  Term coined by C. Nageli and C. Cramer in 1855, and Plasmalemma coined by J. Q. Plowe in 1931.
  • 4. Membrane Structure  Membranes consist of a phospholipid bilayer combined with a variety of proteins in a fluid mosaic arrangement .  The surfaces of cell membranes are hydrophilic (water-loving); the interiors are hydrophobic
  • 5. Some general properties of Plasma Membrane  Keeps a cell intact.  Protective barrier.  Regulate transport in & out of cell (selectively permeable).  Small lipid-soluble molecules, e.g. oxygen and carbon dioxide can pass easily .  Water can freely cross the membrane.  Ions and large molecules cannot cross without assistance .  Allow cell recognition & provide anchoring sites for filaments of cytoskeleton.  Provide a binding site for enzymes.
  • 6. Chemical Composition of Plasma Membrane  Lipids -four major classes of lipids are commonly present in the plasma membrane: phospholipids (most abundant), spingolipids, glycolipids and sterols (e.g. cholesterol). All of them are amphipathic. Cholesterol is abundant in mammalian cell and is absent in prokaryotic cells.  Proteins -plasma membrane contains about 50% protein. Amount and type is variable. Myelin cells contains about 25% protein internal membranes of chloroplast and mitochondria contains 50% protein. Proteins of plasma membranes are of two types ectoproteins and endoproteins. Plasma membranes contains structural proteins, transport proteins and enzymes. Some of them acts as receptors. (enzymes present in the plasma membrane are Acetyl phosphatase, acid phosphatase, ATPase, RNAase,
  • 7.  Carbohydrates- they are present only in the plasma membrane and are present exterior (glycoproteins) or polar end of phospholipids at the external surface of plasma membrane.
  • 8. History of the Plasma Membrane 1895: Charles Overton - Composed of lipids 1925: E. Gorter and G. Grendel - Phospholipid bilayer 1935: J.R. Danielli and H. Davson - Proteins also part, proposed the Sandwich Model 1950’s: J.D. Robertson - Proposed the Unit Membrane Model 1972: S.J. Singer and G.L. Nicolson – Proposed Fluid Mosaic Model
  • 9. Establishment of the Idea of a Cell Barrier  17th century: Invention of microscopes enabled closer examination of various tissues. Upon looking at the tissues under a lens, scientists discovered small, room-like spaces that they gave the name "cells," with barriers between each space. Similar barriers were assumed to exist in animal cells, though they could not be seen.
  • 10. Overton’s model of Plasma Membrane  Overton develops concept of a lipid membrane and according to him a lipid bilayer consists of two apposed lipid monolayers with the hydrophilic lipid head groups facing the surrounding fluid spaces on each side of the bilayer and the hydrophobic lipid hydrocarbon chains localized in the bilayer center. Such an arrangement of lipid molecules represents an ideal functional and structural boundary for cells. The ion gradients across membranes, produced by membrane-embedded ion pumps, are critical to cell functions, including the production of ATP, nerve conduction, and muscle contraction. N N N
  • 11. Phospholipid bilayer model (Gorter & Grendel’s work)  In 1925, Gorter and Grendel, stimulated by the findings of Franklin and Overton, performed a series of studies that had a major impact on all subsequent thinking dealing with membrane structure.  These investigators extracted the lipids from erythrocyte membranes of a variety of species and and then spreading the lipids as a mono-layer in a Langmuir- Blodgett trough and then calculated the area covered by these lipids when spread on water to form a monomolecular layer.  They also approximated the total area of the membranes from which the lipid was extracted and concluded that the area of the monomolecular layer was twice the membrane area; that is, there was sufficient lipid to form a double or bimolecular layer of lipid around the cells, with each layer being about 25 A thick.
  • 12.  Oil spreads at air–water interfaces. a Oil molecules spontaneously spread on the air–water interface until they form a layer one molecule thick. b Langmuir trough allows to precisely measure the surface that these monolayers can spread depending on the applied pressure
  • 13. Based on their observation of their expt. which they did. They hypothesized :-  Cell membranes are made of two opposing thin lipid double layers  Polar head groups pointing toward the aqueous environment (Polar heads face out and Nonpolar tails face in) Surface measurement of membrane lipid monolayers as a way to determine membrane structure. Summary of the method, consisting in the comparison between the area of lipidsextracted from erythrocyte membranes and the estimated surface area of cells. The ratio of 2:1indicated the lipid bilayer structure
  • 14. Sandwich Model (Danielli & Davson Model)  In 1935, Davson and Danielli modified the model proposed by Gorter and Grendel by including protein in the membrane structure.  As because the model provided by Gorter & Grendel could not account for the manifold of functions attributed to cell membranes. (Does not explain why some nonlipids are permeable) and their model could not provide answers to questions on surface tension, permeability, and the electric resistance of membranes.  Therefore, physiologist H. Davson & biologist J. Danielli suggested that membranes indeed do have proteins. According to them, the existence of these "membrane proteins" explained that which couldn't be
  • 15.  Therefore, in 1935 Danielli and Davson proposed a sandwich membrane model (the Davson–Danielli model or the protein–lipid–protein model) in this model, the lipid layer was covered by a thin protein layer on both sides. This observation was significant progress in understanding better the compositional nature of biological membranes.  The Davson-Danielli model immediately became popular, and it dominated cell membrane studies for the following 30 years. There were some light polarization and X-ray diffraction studies to support the model.
  • 16.  In summary, the Davson-Danielli model took into account the difference between the physical properties measured for natural membranes and membranes composed of pure lipids, for example, the low values of surface tension measured in the 1920s and 1930s in plasma membranes compared to lipid bilayers.  However, although the researchers were conscious of the permeability of ions, sugars, and other hydrophilic solutes, the model they postulated implied that the protein layer did not interact with the hydrophobic parts of the lipid bilayer and that the protein layer formed by simple physical adsorption.
  • 18. Unit Membrane model of Plasma Membrane  In 1959, Robertson compared a collection of cross- section pictures and observed that the whole railroad track was consistent in a variety of cells  He thought that the railroad track fit the Davson– Danielli model and extended it as the unit membrane or the Davson– Danielli–Robertson (DDR) model.  Robertson stressed two points in the model: first, that the three layers observed in the electron microscope cross-section shots were part of the same structure, the cell membrane, regardless of the other cell envelopes that might exist; and second, that this structure was universally shared among all biological membranes
  • 19.  The unit membrane model assigned the bilayer structure to all membrane systems, including cell membranes and cellular organelle membranes Unit membrane concept. Railroad track images from thin section electron microscopy of osmium-fixed cells: two dark lines separated by a clear region. Robertson summarized the available data and used many new examples to make the point that all cell membranes have a common structure..
  • 20.  nn Unit Membrane model of Plasma membrane
  • 21. Fluid Mosaic Model of Plasma memb. With the development of the freeze-fracture technique and immuno-electron microscopy, researchers identified antibody-recognizing isolated membrane proteins and proteins that spanned the lipid bilayer.  In 1972, Singer and Nicolson proposed their celebrated fluid mosaic model (FMM) of biological membranes and this model has since been a central paradigm in membrane science.  The basics of the model have remained the same ever since the membrane is a lipid bilayer with hydrophilic parts on the sides and hydrophobic parts in the interior; proteins can interact with surface through transient polar contacts, but a lot of proteins are partially or totally embedded in the lipid bilayer where their hydrophobic parts also interact
  • 22.  Considering the big controversy going on at the beginning of the 1970s, the FMM incorporated for the first time many relevant experimental facts and the development of techniques:- I. The permeability and transport studies that predicted enzyme-like transmembrane proteins. II. The apparent lack and limited transverse mobility of lipids to make up complete bilayers , thus pointing out to the participation of proteins in the membrane plane. III. Electron microscopy pictures,including freeze- etching technique and immuno-EM studies that identified antibody -recognizing isolated membrane proteins. IV. The stability of artificial lipid bilayers that
  • 23. Salient feature of Fluid mosaic model  The specific features and important contributions of the model are demonstrated in detail as follows.  the model recovered the lipid bilayer concept from Danielli and Davson as mentioned above. Membrane lipids are amphipathic. They possess both a hydrophobic and a hydrophilic moiety. Because of this amphipathic character, in an aqueous medium they can organize themselves on both sides of an imaginary plane, with the hydrophobic portions facing each other, and the polar moieties oriented to the outer, aqueous space.  membrane proteins can be associated either to the lipid
  • 24.  both lipids and proteins are in constant motion. In principle, three main of motion could be considered, rotational, translational, and transbilayer.  the asymmetry of membranes has also proven to be a fruitful characteristic.
  • 25. Fluid mosaic model  k Fluid mosaic model
  • 26. Modified Fluid Mosaic Model  In 2005, Engelman proposed an update of the Singer–Nicolson model . He put forward the idea that “membranes are more mosaic than fluid.” Transmembrane proteins are so frequent in membranes that hardly any lipid molecule in the bilayer is left unperturbed. An amended and updated version of the fluid mosaic model with more mosaic proteins.
  • 27.  Apart from the high density of transbilayer proteins in the membrane, he also pointed out three other features that are now considered to occur in most cell membranes. :- I. Integral proteins exist voluminous extramembrane domains. This conclusion has been proved by the increasing data of the three-dimensional structures of many membrane proteins. II. Contacts between proteins are more frequent. This phenomenon is observed in multiple events, for example, G- protein-mediated signaling, in which a receptor protein will physically interact with a G-protein that, in turn, will transiently bind and activate a cyclic ATPase, thus triggering a cellular response to the signal. III. The thickness of the lipid bilayer is uneven. Because the transmembrane portions of intrinsic membrane proteins exhibit a rough surface, and the whole domains have a
  • 28.  This updated model incorporates recent information on both membrane proteins and lipids, containing membrane domains, lipid rafts, and cytoskeletal fencing that were unknown in the 1970s. Schematic illustration of a modification of the fluid mosaic membrane model. Different lipids are indicated in various colors forming specialized domains around integral membrane proteins and glycoproteins as well as being asymmetrically distributed across the membrane.
  • 29. Lipid raft model of Plasma memb.* Simons and Ikonen in 1997 postulated particular functional aspects of specialized domains called lipid rafts in biological membranes.  The lipid raft hypothesis proposes that the lipid bilayer is not a structurally passive solvent, but that the preferential association between sphingolipids, sterols, and specific proteins bestows cell membranes with lateral segregation potential.  The lipid raft model has long suffered controversy since there is little direct quantitative experimental evidence that such domains exist. The traditional method to study lipid rafts and their association with certain membrane proteins is based on the observation of the detergent- resistant membranes (DRMs), composed of mainly sphingomyelin, other saturated phospholipids,
  • 30. Controversies of Lipid raft model  The lipid raft model has long suffered controversy since there is little direct quantitative experimental evidence that such domains exist. The traditional method to study lipid rafts and their association with certain membrane proteins is based on the observation of the detergent-resistant membranes (DRMs), composed of mainly sphingomyelin, other sat. phospholipids, cholesterol, and GPI-anchored proteins  This tech. was severely criticized, because it utilizeddetergents that might induce phase separation and/or affect the partitioning.
  • 31. Strengths and weaknesses of the most common methods for characterization of lipid rafts.
  • 32. Conclusion  With the development of various techniques, our understanding of the structure and function of the cell membranes is more thorough and comprehensive.  Another fact of note is that every achievement made in the field of the cell membrane depends on the development of new techniques and experimental approaches. From traditional methods such as electron microscopy, X-ray crystallograph, fluorescence microscopy, nuclear magnetic resonance spectroscopy, and mass spectroscopy, to modern methods like atomic force microscopy (AFM) all the techniques have provided and will provide the significant information of the membrane structure.  Moreover, we should know that one model cannot fit every cellular membrane under all conditions. Therefore, the cell membrane structure needs to be refined and modified continually and considered on each specific case, such as different cell types and external environments.