Cell

1. REFERENCES
BORON & BOULPAEP MEDICAL PHYSIOLOGY A Cellular &
Molecular Approach. 2nd Edition 2012 by Saunders, Elsevier.
GUYTON & HALL TEXTBOOK OF MEDICAL PHYSIOLOGY A south
Asian Edition. Vaz, Kurpad & Raj. 2013 Elsevier
GANONG’S REVIEW OF MEDICAL PHYSIOLOGY
24 Edition Tata McGraw 2012
FACILITATOR: Dr. Paul Mungai Mbugua (PMM)
Department of Medical Physiology
College of Health Sciences
University of Nairobi
Email: pmungai@uonbi.ac.ke

2. TITLE OF TOPICS TO BE COVERED
CELL MEMBRANE (CM):
STRUCTURE
PROPERTIES
FUNCTIONS
TRANSPORT ACROSS
ENDOPLASMIC RETICULUM
CYTOSKELETON
CELLULAR COMMUNICATION

3. CELL MEMBRANE (CM)
Plasma Membrane (PM)
Crucial to the life of the cell
Encloses the cell
Defines its boundaries
Maintains the essential differences between
the cytosol & the extracellular environment

4. Extracellular
Concentration [X]o
Intracellular
Concentration [X]i
Na+ 145 mM 15 mM
K+ 4.5 mM 120 mM
Ca2+ 1.2 mM 10-7 M
Cl- 116 mM 20 mM
HCO-
3 25 mM 16 mM
Protein 2 g/dL 16 g/dL

5. CELL MEMBRANE (CM)
Highly fluid, dynamic structure
Thin, flexible, elastic structure – 7.5 to 10
nanometers (nm) thick
Lipids & Proteins
Endoplasmic reticulum, mitochondria,
lysosomes, Golgi apparatus
Selective membrane molecular permeability

7. CM LIPIDS
Belong to the molecular family of
PHOSPHOLIPIDS
Most important PROPERTIES associated with:
UNIQUE STRUCTURE
PHYSICAL CHEMISTRY
Shape of the phospholipid molecule reflects
SOLUBILITY PROPERTIES

13. “HEAD” END OF PHOSPHOLIPID MOLECULE
In most phospholipids present in CMs, the
phosphate is esterified to an alcohol such as:-
CHOLINE
ETHANOLAMINE
GLYCEROL
INOSITOL
SERINE

14. “HEAD” END OF PHOSPHOLIPID MOLECULES
Determines the name of phospholipid:-
PHOSPHATIDYLETHANOLAMINE
PHOSPHATIDYLINOSITOLS
PHOSPHATIDYLSERINES
PHOSPHATIDYLCHOLINES
Many of the properties of phospholipids

15. “HEAD” END OF PHOSPHOLIPID MOLECULES
Contains the phosphate portion
Charged or Polar
Very water soluble
Interact well with water at both membrane
surfaces
HYDROPHILIC

16. FATTY ACIDS (FAs)
Lack charged groups that would facilitate
interactions with water, which is polar
Dissolve poorly in water – nonpolar molecules
Dissolve readily in organic solvents
HYDROPHOBIC GROUPS OR “TAILS” ends
of phospholipid molecules

17. AMPHIPATHIC
All major lipids in membranes contain both
HYDROPHOBIC and HYDROPHILIC regions
and are therefore termed AMPHIPATHIC
When mixed with water, HYDROPHILIC head
groups are fully dissolved in water
AMPHIPHILIC

20. MONOLAYER
Form a MONOLAYER at air-water interface at
fairly low concentrations

21. MICELLES
At higher concentrations, assemble
spontaneously to form MICELLES

26. MICELLE
Small spheres - ~ 200 nm
HYDROPHILIC groups form the surfaces of the
small spheres
HYDROPHOBIC tails point toward their centers
HYDROPHOBIC regions are protected from any
contact with water

27. BIMOLECULAR LIPID BILAYER
At much higher concentrations,
phospholipids spontaneously form
BIMOLECULAR LIPID BILAYER

31. PHOSPHOLIPID BILAYER
An individual phospholipid molecule is FREE to
diffuse in the plane of bilayer – LATERAL
DIFFUSION
Rate at which the two- dimensional diffusion
occurs is extremely TEMPERATURE -
DEPENDENT

32. PHOSPHOLIPID BILAYER
Transverse movement of phospholipids across
the CM (flip-flop) is extremely slow

33. FLUID MOSAIC MODEL OF CM
At normal body temp (37°C), the lipid bilayer is
in a FLUID STATE-LIQUID-LIKE
Fluidity of CM largely depend upon lipid
composition of the CM
Hydrophobic FA chains can be highly aligned or
ordered to provide a rather STIFF STRUCTURE

34. FLUIDITY OF CM
Significantly affects its FUNCTION
As MEMBRANE FLUIDITY INCREASES:-
Permeability to water increases
Permeability to small hydrophilic molecules
increases
Lateral mobility of integral proteins increases
Receptor proteins binds more ligands

36. CHOLESTEROL
Most common STEROL in CM
MAJORITY of cholesterol resides in CMs
Smaller amounts are found in the mitochondrial,
Golgi complex, & nuclear membranes

37. CHOLESTEROL
HYDROPHILIC hydroxyl group interacts with
phospholipids at the aqueous interface
HYDROPHOBIC portion interacts with FA
chains
Substantially disrupt the ability of phospholipids
to interact among themselves

38. CHOLESTEROL
PARTIALLY IMMOBILIZES FA side chains
DECREASES CM fluidity at low concentrations
INCREASES CM fluidity at high concentrations

40. MEMBRANE PROTEINS
Associated with LIPID BILAYER
Proteins can be AMPHIPATHIC
HYDROPHILIC regions of membrane proteins
protrude at the inside & outside faces of the CM
HYDROPHOBIC regions of membrane proteins
traverse the hydrophobic core of the CM
HYDROPHOBIC AMINO ACIDS of membrane
proteins are located in the hydrophobic core of the CM

41. MEMBRANE PROTEINS
There are HUNDREDS of proteins in the CM
Proteins are the MAJOR FUNCTIONAL MOLECULES
of the CM
Membrane proteins consist of:-
ENZYMES
PUMPS
TRANSPORTERS
CHANNELS
STRUCTURAL COMPONENTS
ANTIGENS
RECEPTORS
Every type of CM possesses a DIFFERENT
COMPLEMENT of proteins

42. TWO TYPES OF MEMBRANE PROTEINS
PERIPHERAL MEMBRANE PROTEINS
INTEGRAL MEMBRANE PROTEINS
Most membrane proteins fall into the INTEGRAL
CLASS, meaning that they interact extensively with the
PHOSPHOLIPIDS
Integral proteins are AMPHIPATHIC
Consist of TWO HYDROPHILIC ENDS separated by
an intervening HYDROPHOBIC region that traverses
the hydrophobic core of the CM

43. INTEGRAL MEMBRANE PROTEINS
The following integral membrane proteins SPAN the
CM many times:-
TRANSPORTER MOLECULES
ION CHANNELS
VARIOUS RECEPTORS
G PROTEINS
TRANSMEMBRANE PROTEINS

44. INTEGRAL MEMBRANE PROTEINS
Some integral membrane proteins are EMBEDDED in
the CM without actually crossing it
COVALENT BONDS link integral proteins to FATTY
ACID components of phospholipids
Some simple integral membrane proteins SPAN the CM
ONLY ONCE

46. PERIPHERAL MEMBRANE PROTEINS
DO NOT INTERACT DIRECTLY with the hydrophobic
cores of the phospholipids in the CM
Are bound to the HYDROPHILIC regions of:
HEAD GROUPS OF PHOSPHOLIPIDS
SPECIFIC INTEGRAL PROTEINS
ADHERE TIGHTLY to the cytoplasmic or extracellular
surfaces of CM

47. PERIPHERAL MEMBRANE PROTEINS
They are NOT EMBEDDED within the CM
They are NOT ATTACHED to the CM by COVALENT
BONDS-(NONCOVEMENT BONDS) (attached loosely)
They use IONIC & HYDROGEN BONDS to closely
ASSOCIATE with the CM - (ionic interactions)

48. FUNCTIONS OF INTEGRAL MEMBRANE PROTEINS
SERVE AS RECEPTORS
SERVE AS ADHESION MOLECULES
CARRY OUT THE TRANSMEMBRANE
MOVEMENT OF WATER-SOLUBLE
SUBSTANCES
SERVE AS ENZYMES
PARTICIPATE IN INTRACELLULAR
SIGNALING

49. CELL MEMBRANE RECEPTORS
Perfectly situated to transmit signals –
TRANMEMBRANE SIGNALING
LIGAND-BINDING RECEPTORS
HIGH-AFFINITY BINDING SITES
Produce CONFORMATIONAL CHANGES within
the transmembrane receptor protein
Intracellular domain either becomes
enzymatically active or interact with cytoplasmic
proteins to generate second messengers
TRANSMEMBRANE SIGNAL TRANSDUCTION

50. LIGAND-BINDING RECEPTOR
Transmit signals from the outside to the inside
of a cell
The ligand may be:-
Hormone
Growth factor
Neurotransmitter
Paracrine
Autocrine

52. ADHESION MOLECULES
Adhesion molecules interact with surrounding
EXTRACELLULAR MATRIX – CELL-MATRIX
ADHESION MOLECULES
Adhesion molecules interact with CELLULAR
NEIGHBORS – CELL-CELLADHESION
MOLECULES
Cell-matrix adhesion molecules & cell-cell adhesion
molecules are extremely important in regulating the:
SHAPE of cells
GROWTH of cells
DIFFERENTIATION of cells
Direct migration of immune cells
Guide axons in developing nervous system

53. INTEGRINS
Large family of transmembrane proteins that
link cells to components of the extracellular
matrix such as fibronectin and laminin
Are matrix receptors or cell matrix adhesion
molecules

55. CELL-CELLADHESION MOLECULES
Superfamily of transmembrane proteins that
attach CELL TO EACH OTHER
Include the Ca2+-dependent cell adhesion
molecules (cadherins)
Include Ca2+-independent neural cell adhesion
molecules (N-CAMs)
Cadherins & N-CAMs mediate transmembrane
signals that help organize the cytoplasm &
control gene expression in response to
INTERCELLULAR contacts
Loss of cell-cell & cell-matrix adhesion
molecules is a hallmark of METASTATIC
TUMOR CELLS

56. INTRINSIC MEMBRANE PROTEINS THAT FORM PORES
Specialized aqueous transmemberane conduit
that are always OPEN
NONGATED CHANNELS
Allow vast number of particles to cross the
CM
No conformational states involved
Three examples:
PORINS
PERFORINS
AQUAPORINS

58. PORINS
Large size pores
Found in the outer membranes of gram
negative bacteria & mitochondria
Mitochondrial porin allow solutes to diffuse
passively from the cytosol into the
mitochondria’s intermembrane space

59. PERFORINS
Pore forming protein released by cytotoxic T
lymphocytes
Polymerize within the target CM forming
pores
Passive flow of ions, water & small molecules
through perforins kills the target cell

60. NUCLEAR PORE COMPLEX
Contain SIMPLE AQUEOUS PORES
Allow small molecules to move between the
cytoplasm & the nucleus

61. AQUAPORINS
Located on the CM of many types of cells
Allow WATER MOLECULES to pass
through

62. INTRINSIC MEMBRANE PROTEINS
THAT FORM CHANNELS
Open to both ICF & ECF simultaneously
Alternately OPEN & CLOSE
GATED refers to presence of a movable barrier
Allow multiple ions to cross the CM passively
per open event
Undergo conformational transitions between
closed & open states
Some channels contain solute-binding sites
within their permeation pathways
Fundamental event is OPENING

63. EXAMPLES OF CHANNELS
Physiological examples include virtually all
ion channels:-
Na+ CHANNEL
CI- CHANNEL
K+ CHANNEL
Ca2+ CHANNEL