MEMBRANES

Marie Clare V. Robles, M.D.

MCU-FDTMF COLLEGE OF MEDICINE
DEPARTMENT OF BIOCHEMISTRY
 MEMBRANES
 Highly viscous, plastic structures
that form closed compartments
around cellular protoplasm to
separate the cytoplasm from the
outside environment.
THE FUNCTIONS OF CELL MEMBRANES
THE FUNCTION OF CELL MEMBRANES
 It determines the boundaries of the cell, and thus
influences their size and shape.
 It provides a surface for some enzyme reactions.
 It controls movement of nutrients, metabolites,
and other solutes in and out of the cell.
 It contains receptors for signal molecules
(such as hormones).
 It carries cell recognition sites (cell surface
glycoproteins) that are involved in cell-cell
recognition.
THE BODY’S INTERNAL WATER

 Water makes up 60% of the lean

body mass
 COMPARTMENTS:
 IntracellularFluid (ICF)
 Extracellular Fluid (ECF)
INTRACELLULAR FLUID (ICF)
 2/3 of total body water
 Provides the environment of the
cell to:
1. make, store & utilize energy
2. repair itself
3. perform special functions
4. replicate
EXTRACELLULAR FLUID (ECF)
 1/3 of total body water
 Distributed between plasma & interstitial
compartments
 A delivery system
it brings to the cell nutrients, O2, various ions &
trace minerals & a variety of regulatory
molecules that coordinate the functions of
widely separated cells.
 Removes CO2, waste products & toxic or
detoxified materials from the immediate
cellular environment
COMPARISON OF MEAN CONCENTRATION OF
VARIOUS SUBSTANCES OUTSIDE & INSIDE A
MAMMALIAN CELL
SUBSTANCES ECF ICF
Na+ 140 mmol/L 10 mmol/L
K+ 4 mmol/L 140 mmol/L
Ca2+ (free) 2.5 mmol/L 0.1 umol/L
Mg2+ 1.5 mmol/L 30 mmol/L
Cl- 100 mmol/L 4 mmol/L
HCO3- 27 mmol/L 10 mmol/L
PO4- 2 mmol/L 60 mmol/L
Glucose 5.5 mmol/L 0-1 mmol/L
Protein 2 g/dL 16 g/dL
COMPARISON OF MEAN CONCENTRATION OF
VARIOUS SUBSTANCES OUTSIDE & INSIDE A
MAMMALIAN CELL
SUBSTANCES ECF ICF
Na+ 140 mmol/L 10 mmol/L
K+ 4 mmol/L 140 mmol/L
Ca2+ (free) 2.5 mmol/L 0.1 umol/L
Mg2+ 1.5 mmol/L 30 mmol/L
Cl- 100 mmol/L 4 mmol/L
HCO3- 27 mmol/L 10 mmol/L
PO4- 2 mmol/L 60 mmol/L
Glucose 5.5 mmol/L 0-1 mmol/L
Protein 2 g/dL 16 g/dL
COMPARISON OF MEAN CONCENTRATION OF
VARIOUS SUBSTANCES OUTSIDE & INSIDE A
MAMMALIAN CELL
SUBSTANCES ECF ICF
Na+ 140 mmol/L 10 mmol/L
K+ 4 mmol/L 140 mmol/L
Ca2+ (free) 2.5 mmol/L 0.1 umol/L
Mg2+ 1.5 mmol/L 30 mmol/L
Cl- 100 mmol/L 4 mmol/L
HCO3- 27 mmol/L 10 mmol/L
PO4- 2 mmol/L 60 mmol/L
Glucose 5.5 mmol/L 0-1 mmol/L
Protein 2 g/dL 16 g/dL
COMPOSITION OF
BIOLOGIC MEMBRANES
LIPIDS
PROTEINS
CARBOHYDRATES
 MEMBRANE LIPIDS

 PHOSPHOLIPIDS
 GLYCOSPHINGOLIPIDS
 STEROLS
 MEMBRANE LIPIDS

 PHOSPHOLIPIDS
PHOSPHOGLYCERIDES
• More common
 Phosphatidylcholine
 Phosphatidylethanolamine

 Phosphatidylserine

SPHINGOMYELIN
 MEMBRANE LIPIDS

 GLYCOSPHINGOLIPIDS
 Sugar-containing
lipids built
on a backbone ceramide
 Cerebrosides

 Gangliosides
STEROLS
 STEROLS
 cholesterol serves to "buffer" extreme
fluidity changes
• At temps. below the transition temperature
("melting" midpoint) of membrane, cholesterol
insertion prevents snug highly ordered packing
of phospholipid "tails" so increases fluidity.
• At temps. above the thermal transition
temperature, rigid ring system of sterol
reduces freedom of neighboring "tails" to
rotate about their C-C bonds, so reduces
fluidity in core of bilayer.
MEMBRANE LIPIDS
 AMPHIPATHIC
 MEMBRANE LIPIDS
 FORM BILAYERS
 LIPID BILAYERS
(Bimolecular layer)
Key structures in biologic
membranes
LIPID
BILAYERS

 Satisfythe thermodynamic requirements of

amphipathic molecules in an aqueous
environment.
 exist as a sheet, hydrophobic regions of the
phospholipids are protected from aqueous
environment, hydrophilic regions are immersed in
water.
 LIPID BILAYERS
 Self-assembly
 By hydrophobic effect
 When lipid molecules come together in
bilayer, the entropy of the surrounding
solvent molecules increases.
PERMEABILITY COEFFICIENT IN
LIPID BILAYER MEMBRANES
Permeability of the BLM
mol/sec-sq. cm.
MEMBRANE PROTEINS ARE
ASSOCIATED WITH THE LIPID
BILAYER
 Major functional molecules of
membranes
 Consist of:
 Enzymes
 Pumps and channels
 Structural components
 Antigen (eg, for histocompatibility)
 Receptors for various molecules
ENZYMATIC MARKERS OF
DIFFERENT MEMBRANES
MEMBRANE ENZYME
PLASMA 5’-Nucleotidase
Adenylyl cyclase
NA+–K- ATPase
ENDOPLASMIC RETICULUM Glucose-6-phosphatase
GOLGI APPARATUS
CIS GlcNAc transferase I
MEDIAL Golgi mannosidase II
TRANS Galactosyl transferase
TGN (TRANS GOLGI NETWORK) Sialyl transferase
INNER MITOCHONDRIAL ATP synthase
MEMBRANE
MEMBRANES ARE
ASYMMETRIC STRUCTURES
 Partially attributed to the irregularity
of membrane proteins.
 An inside-outside asymmetries
 provided by external location of
carbohydrate attached to membrane
proteins.
 Location of specific enzymes
 Phospholipids
MEMBRANES ARE
ASYMMETRIC STRUCTURES
 MEMBRANE PROTEINS
 Perform most of the enzymatic,
transport and recognition functions of
membranes.
 CLASSES:
INTEGRAL(INTRINSIC)
PERIPHERAL (EXTRINSIC)
MEMBRANE PROTEINS
 INTEGRAL PROTEINS
 Embedded in the lipid bilayer
 Globular, amphipathic

 Interact extensively with the

phospholipids
 Only drastic measures for them to be
removed from the membrane (use of
detergents or organic solvents)
MEMBRANE PROTEINS
 PERIPHERAL PROTEINS
 Associate only with the surface of
membrane
 Do not interact directly with the
phospholipids in the bilayer
 Can be removed easily, does not require
the use of detergents for their release
MEMBRANE PROTEINS

PERIPHERAL INTEGRAL
PROTEIN PROTEINS
MEMBRANE CARBOHYDRATES

 Least amount
 as Glycolipids and Glycoproteins
 THE FLUID MOSAIC MODEL
OF MEMBRANE STRUCTURE
PROPOSED IN 1972 BY
SINGER & NICOLSON
THE FLUID MOSAIC MODEL

 Lipid bilayer
 Cholesterol between tails
 Protein, Glycoprotein,
Lipoprotein “dissolved” in
the lipid portion
THE FLUID
MOSAIC MODEL

MEMBRANE
MOTION
“TRANSITION TEMPERATURE” (TM)
 FLUIDITY OF MEMBRANES
 Lipids undergo physical changes in state at
increased temperature order-disorder transitions
 The temperatures at which these changes take place
TRANSITION or MELTING TEMPERATURES (Tm)
 Below the Tm
 the lipid assumes a gel-like solid structure  loses its
fluidity
 the chains are almost all in an extended conformation, in
which every carbon-carbon bond is in an anti-
conformation  gives the chains and the resulting
membrane its greatest thickness
 Above the Tm
 the chains assume random conformations and can also
intercalate between each other
 MEMBRANE FLUIDITY
 TEMPERATURE
 FATTY ACID CHAIN LENGTH
 DEGREE OF UNSATURATION
OF FATTY ACIDS
 CONTENT OF CHOLESTEROL
The membrane is fluid
The membrane is fluid
The membrane is fluid
The membrane is fluid
Cholesterol sits between fatty tails
Proteins can span the bilayer
Hydrophilic

Hydrophobic
MEMBRANE SELECTIVITY ALLOWS
SPECIALIZED FUNCTIONS
 Cross-membrane movement of small
molecules
 Diffusion (passive and facilitated)
 Active transport
 Cross-membrane movement of large
molecules
 Endocytosis
 Exocytosis
 Signal transmission across membranes
 Cell surface receptors
1. Signal transduction (eg, glucagon  AMP)
2. Signal internalization
 Movement to intracellular receptors (steroid hormones)
 Intercellular contact and communication
DIFFUSION
 Passive, spontaneous movement of
molecules through the bilayer down an
electrochemical gradient.
 Factors affecting net diffusion of a
substance:
 Its concentration gradient across the
membrane.
 The electrical potential across the membrane.
 The permeability coefficient of the substance
for the membrane.
 The hydrostatic pressure across the
membrane.
 Temperature.
ION CHANNELS ARE TRANSMEMBRANE
PROTEINS THAT ALLOW THE SELECTIVE
ENTRY OF VARIOUS IONS

 The permeability of channels

depends upon:
 Size
 Extent of hydration
 Extent of charge density on the ion

 Activity of some ion channels is

controlled by neurotransmitter.
Channels are open transiently and
thus are “gated”
 LIGAND-GATED CHANNELS
 A specific molecule binds to
a receptor and opens the
channel.

 VOLTAGE-GATED
CHANNELS
 Open (or close) in response
to changes in membrane
potential.
 TRANSPORT SYSTEMS
 UNIPORT SYSTEM
 Moves one type of molecule bidirectionally
 CO-TRANSPORT SYSTEMS
 the transfer of one solute depends upon
the stoichiometric simultaneous or
sequential transfer of another solute.
 SYMPORT moves these solutes in the
same direction.
 ANTIPORT moves 2 molecules in opposite
directions
TRANSPORT SYSTEMS
Carrier protein transfer molecules into or out
of the cell through this 2 types of processes:

 FACILITATED DIFFUSION
 ACTIVE TRANSPORT
FACILITATED DIFFUSION &
ACTIVE TRANSPORT
SIMILARITIES:
 Both appear to involve carrier proteins.
 Show specificity for ions, sugars and amino
acids.
 A specific binding site for the solute.
 The carrier is saturable.
 There is a binding constant for the solute.
 Structurally similar competitive inhibitors block
transport.
FACILITATED DIFFUSION &
ACTIVE TRANSPORT
DIFFERENCES:
 Facilitated diffusion can operate
bidirectionally, Active transport usually
unidirectional
 Active transport always occurs against
an electrical or chemical gradient 
requires ENERGY.
A “Ping-Pong” Mechanism of
Facilitated Diffusion
 A protein carrier in the lipid bilayer
associates with a solute in high
concentration on one side of the membrane.
 A conformational change ensues (“pong” to
“ping”), solute is discharged on the side
favoring the new equilibrium.
 The empty carrier then reverts to the original
information (“ping” to “pong”) to complete
the cycle.
 Process is completely reversible
 Net flux across the membrane depends upon 1. the
concentration gradient 2. the amount of carrier
available 3. rapidity of solute –carrier interaction 4.
rapidity of conformational change for loaded and
unloaded carrier
The “Ping-Pong” Model of
Facilitated Diffusion
Cells transport macromolecules
across the plasma membrane by:
 ENDOCYTOSIS
 Process by which cells take up large
molecules.
 Responsible for the entry of DNA
into the cell.
 Requires:
 Energy

 Calcium in the ECF

 Contractile elements in the cell
(microfilament system)
ENDOCYTOSIS
 General types:
 PHAGOCYTOSIS
 Occurs in specialized cells
(macrophages & granulocytes).
 Involves ingestion of large particles
(virus, bacteria & debris).
 PINOCYTOSIS
A property of all cells.
 Leads to the cellular uptake of fluid &
fluid content.
EXOCYTOSIS
 The process by which
macromolecules are released to the
exterior of the cell.
 Involved in membrane remodelling.
 Triggered by the presence of
calcium.
EXOCYTOSIS
 Molecules released by exocytosis
fall into three categories:
 They can attach to the cell surface
and become peripheral proteins
(antigens).
 They can become part of the ECM
(collagen & glycosaminoglycans).
 They can enter ECF and signal
other cells.
THE
END