TRENDS IN CELL BIOLOGY

ABS-931

3(3-0)

Course Contents:

• Introduction

• Cell Organization

• Cell Architecture

• Membrane Structure and Function

• Bio Transport

• Vesicular Transport

• Transport Signals

• Nuclear Transport

• Bio Energetic

• Mitochondrial Energy Conversion

• Chloroplast Energy Conversion

• Cytoskeleton

• Cell Shape

• Cell Contractility

• Cell to cell Communication

• Electrochemical Signaling

• Synaptic and Sensory Transduction

• Biochemical Signaling

• Receptor Ligand Interactions

• Second Messengers

• Signaling Cascades

• Cell Cycle and Apoptosis

• Phases of Cell Cycle and Cell Division

• Regulation of Cell Growth and Death

• Specialized Cell Systems

Recommended Books:

• The Cell by Bruce Albert and Dennis Bray, 4th Ed. Garland

Publishing Inc, New York and London.

• Biochemistry by Victor L. Davidson, Donald B. Sittman. 3rd Ed.

1993, Harwal Pub Co.

• Cell and Molecular Biology by Gerald Karp. 1996, John Willey

and Sons, Inc. London

• Gene VIII By Lewin Benjamin Eds 2004. Oxford University

press, Inc, New york.

• Molecular Biology of the Gene by Watson, J. D., T. A. Baker, S.

P. Bell, A. Gann, M. Levine, and R. Losick, 5th Ed. 2003. New

York, Benjamin Cummings ISBN 0-8053-4635-X

Policies

First 1 hr Test 17.5 %

Second 1 hr Test 17.5 %

Assignments (3-6) 5-10 %

Quizzes (3-6) 5-10 %

Terminal Exam (3 hrs) 50 %

• Please turn off your cell phones during class

What is cell Biology?

What is cell Biology?

Divisions in the biological sciences are based on

degrees of “complexity”

Biochemistry & Biophysics: study of

the structures and behaviors of

molecules

Microbiology: study of prokaryotic cells

and viruses

Cell Biology: study of the structure

and function of eukaryotic cells

Developmental Biology: study of how

communities of cells form tissues, organs,

and build an organism

Anatomy & Physiology: study of the

structures and functions of tissues and

organs

Zoology & Plant Biology: study of the

organisms

Ecology: study of how organisms interact

with each other and with their environments

Levels of Biological Complexity

1. Biochemistry & Biophysics

2. Microbiology

3. Cell Biology

4. Developmental Biology

5. Anatomy & Physiology

6. Zoology & Plant Biology

7. Ecology

Understanding cell biology is important to

understand the basis for disease

• Hypercholesterolemia (defective uptake of lipoproteins)

• Cystic fibrosis (misfolding of key protein)

• Hypertension (defective cell-cell adhesion in the kidney)

• Congenital heart defects (errors in cell migration during development)

• Muscular dystrophy (defective attachment of the plasma membrane to

the cytoskeleton)

• Lysosomal storage disease (defective intracellular transport of enzymes)

• Food-borne illness (Salmonella, E. coli)

• Cancer (errors in cell division, migration, cell polarity, growth, etc)

• Ageing

• All disease states are caused at the cellular level

Understanding cell biology is important to

make informed decisions on social issues

• Genetic engineering of foods

• Biotechnology

• Organ growth in culture

• Stem cell research

• Forensic sciences

• Archaeology

The Dynamic CellBasic unit of organization or

structure of all living matter

CELL BIOLOGY

Galileo Galilei (Early Seventeenth century) used lenses

Beginning of the study of cells as the basis of life

Robert Hooke (Middle of Seventeenth century) microscopic

examination of sliced cork

Used Latin word cella (small room)

Anton van Leeuwenhoek (Late Seventeenth century)

Improved lenses, Improved magnification

Robert Brown (1831) observed nucleus as opaque spot

Methias Schleiden (1838)

Theodore Schwann (1839)Cell Theory

A brief History

Cell theory, definitions

"Cells are of universal occurrence and are

the basic units of an organism“

Rudolf Virchow (1859)

All cells come from pre-existing cells

During 20th century

A.G. Loewy and P. Siekevitz (1963)

“a unit of biological activity delimited by a semipermeable

membrane and capable of self-reproduction in a medium free of

other living systems”

Wilson and Morrison (1966) “an integrated and continuously

changing system”

John Paul (1970) “the simplest integrated organization in living

systems, capable of independent survival”.

Principles of Cell Theory

• All living things are made of cells

• Smallest living unit of structure and function of all

organisms is the cell

• All cells arise from preexisting cells

(this principle discarded the idea of

spontaneous generation)

Cell Size

Cells Have Large Surface

Area-to-Volume Ratio

Common functional and structural properties of cells

1. Plasma membrane

The plasma membrane forms a boundary between the living cell and its

surroundings.

The plasma membrane regulates the passage of materials into and out of the

cell.

2. Cytoplasm (solution portion CYTOSOL)

Chemical reactions take place in the cytoplasm transforming the energy and

material needed for cell growth and reproduction.

The cytoplasm consists of a soluble, called cytosol, and various particulate

structures.

3. Genetic material

Each cell contains a copy of the hereditary information.

4. Ribosomes

5. Utilizes energy from ATP

Each cell utilizes energy from ATP, the universal energy currency” of living

cells. Cells carry out metabolism through which they generate ATP and cell

constituents for growth and reproduction.

Cell Types

• Prokaryotic

• Eukaryotic

Prokaryotic cell

Eukaryotic cell

Cell Organization

Prokaryotic cells• First cell type on earth

• Single cell organisms

• Two main types: bacteria and archaea

• Relatively simple structure

• No membrane bound nucleus

• Nucleoid = region of DNA concentration

• Organelles not bound by membranes

Eukaryotic cells • Single cell or multicellular organisms

• Plants and animals

• Structurally more complex: organelles,

cytoskeleton

• Nucleus bound by membrane

• Include fungi, protists, plant, and animal

cells

• Possess many organelles

Representative Animal Cell

Representative Plant Cell

Organelles

• Cellular machinery

• Two general kinds

– Derived from membranes

– Bacteria-like organelles

Bacteria-Like Organelles

• Derived from symbiotic bacteria

• Ancient association

• Endosymbiotic theory

– Evolution of modern cells from cells & symbiotic

bacteria

Prokaryotic cells vs Eukaryotic cell

1. Eukaryotic cells have a true nucleus, bound by a double membrane. Prokaryotic cells

have no nucleus.

2. Eukaryotic DNA is linear; prokaryotic DNA is circular (it has no ends).

3. Eukaryotic DNA is complexed with proteins called "histones," and is organized into

chromosomes; prokaryotic DNA is "naked," meaning that it has no histones associated

with it, and it is not formed into chromosomes. A eukaryotic cell contains a number of

chromosomes; a prokaryotic cell contains only one circular DNA molecule and a varied

assortment of much smaller circlets of DNA called "plasmids." The smaller, simpler

prokaryotic cell requires far fewer genes to operate than the eukaryotic cell.

4. Both cell types have ribosomes, but the ribosomes of the eukaryotic cells are larger and

more complex than those of the prokaryotic cell.

5. The cytoplasm of eukaryotic cells is filled with a large, complex collection of organelles,

many of them enclosed in their own membranes; the prokaryotic cell contains no

membrane-bound organelles which are independent of the plasma membrane. Many of

these structures, like the nucleus, increase the efficiency of functions by confining them

within smaller spaces within the huge cell, or with communication and movement within

the cell.

Comparison of features of prokaryotic and eukaryotic cells

Prokaryotes Eukaryotes

Typical organisms Bacteria, Archaea Protists, Fungi, Plants and Animals

Typical size ~ 1-10 µm ~ 10-100 µm (Sperm cells are smaller)

Type of nucleus nucleoid region real nucleus with double membrane

DNA circular (usually)linear molecules (chromosomes) with histone

proteins

RNA-/protein-

synthesiscoupled in cytoplasm

RNA-synthesis inside the nucleus

protein synthesis in cytoplasm

Ribosomes 50S+30S 60S+40S

Cytoplasmatic

structurevery few structures

highly structured by endomembranes and a

cytoskeleton

Cell movement flagella made of flagellin flagella and cilia made of tubulin, lamellipodia

Mitochondria Noneone to several thousand (though some lack

mitochondria)

Chloroplasts None in algae and plants

Organization usually single cellssingle cells, colonies, higher multicellular

organisms with specialized cells

Cell division Binary fission Mitosis (fission or budding), Meiosis

Eukaryotic Cells Evolved from a

Symbiosis

• As predators (engulfing eubacteria)

by animal cells

– Origin of Mitochondria from aerobic

bacteria

• From hunting to Farming

(engulfing photosynthetic bacteria)

by plant cells

– Chloroplast origin

• Scavengers (from hunters) feed on

other cells

– Fungi: Do not posses chloroplast

but cell wall

Us vs. Them -

Eukaryotes and

Prokaryotes

Internal Organization of the cell

Common functional and structural

properties of cells

1. Plasma membrane

2. Cytoplasm (solution portion CYTOSOL)

3. Genetic material

4. Ribosomes

5. Utilizes energy from ATP

Major Divisions of the Eukaryotic Cell

The Plasma Membrane – Gateway to the Cell

Plasma Membrane

• Crucial to the life of the cell,

– encloses the cell,

– defines its boundaries, and

– maintains the essential differences between the cytosol and the

extracellular environment.

• Inside eukaryotic cells, the membranes of the endoplasmic

reticulum, Golgi apparatus, mitochondria, and other membrane-

enclosed organelles maintain the characteristic differences

between the contents of each organelle and the cytosol.

• Ion gradients across membranes, established by the activities of

specialized membrane proteins, can be used

– to synthesize ATP,

– to drive the transmembrane movement of selected solutes, or,

– in nerve and muscle cells, to produce and transmit electrical signals.

• In all cells, the plasma membrane also contains proteins that

act as sensors of external signals, allowing the cell to

change its behavior in response to environmental cues; these

protein sensors, or receptors, transfer information rather

than ions or molecules across the membrane.

• Despite their differing functions, all biological membranes

have a common general structure: each is a very thin film of

lipid and protein molecules, held together mainly by

noncovalent interactions.

• Cell membranes are dynamic, fluid structures, and most of

their molecules are able to move about in the plane of the

membrane.

• The lipid molecules are arranged as a continuous double

layer about 5 nm thick.

• This lipid bilayer provides the basic fluid structure of the

membrane and serves as a relatively impermeable barrier to

the passage of most water-soluble molecules.

• Protein molecules that span the lipid bilayer mediate nearly

all of the other functions of the membrane, transporting

specific molecules across it, for example, or catalyzing

membrane-associated reactions, such as ATP synthesis.

• In the plasma membrane, some proteins serve as structural

links that connect the cytoskeleton through the lipid bilayer

to either the extracellular matrix or an adjacent cell, while

others serve as receptors to detect and transduce chemical

signals in the cell's environment.

• It takes many different membrane proteins to enable a cell to

function and interact with its environment.

• In fact, it is estimated that about 30% of the proteins that are

encoded in an animal cell's genome are membrane proteins.

Membrane functions

1. Compartmentalization

1. Allows specialized activities to proceed without

external interference

2. Enables cellular activities to be regulated

independently

3. Prevents mixing of various contents

2. Providing a selectively permeable membrane

1. Prevents free interchange o material to-and-fro

2. Provides means of communication between spaces

3. PM ensures the entry of appropriate substance into cytoplasm and

inappropriate substance are kept out (selectively permeable)

3. Transporting solutes

1. Physical transport of substances into and out of cell

2. Accumulation of sugars and amino acids necessary to fuel its metabolism

and build its macromolecules

4. Responding to external signals

1. Transfer of information from one side to other through ligand receptor interaction (signal transduction)

5. Intracellular interactions

1. PM mediates interaction between the cells

2. Recognition, adherence and exchange of material and information between cells

6. Scaffolding of biochemical activities

1. Provide framework for effective interaction of components

2. Localization of enzymatic machinery

7. Energy transduction

1. Energy conversion of

1. Sunlight to chemical energy contained in carbohydrates (photosynthesis)

2. Transfer of chemical energy from carbohydrates and fats into ATP (in mitochondria and chloroplast)

2. Sites of energy storage to run cellular activities

Small molecules and larger hydrophobic molecules move through.

Ions, hydrophilic molecules larger than water, and large molecules such as

proteins do not move through the membrane on their own.

The physical properties of phospholipids account for membrane

assembly and many of its properties.

The Plasma Membrane is Semipermeable

History of structure of cell membrane

a) Davidson-Daniellimodel (1954)

b) The Fluid Mosaic model (Singer & Nicolson, 1972)

c) Current representation of Plasma Membrane

Membrane Components

Plasma membrane

• Cytosolic face (internal face)

• Exoplasmic face (external face)

• What about organelles?

– Lysosome -

– Mitochondria –

– Chloroplast –

– Nucleus –

– Vacuole –

Membrane Lipids

• Amphipathic Molecules, most of which spontaneously form

bilayers

• Lipid that is, fatty molecules constitute about 50% of the mass

of most animal cell membranes, nearly all of the remainder

being protein.

• There are approximately 5 × 106 lipid molecules in a 1 mm × 1

mm area of lipid bilayer, or about 109 lipid molecules in the

plasma membrane of a small animal cell.

• All of the lipid molecules in cell membranes are amphipathic (or

amphiphilic) that is, they have a hydrophilic ("water-loving") or

polar end and a hydrophobic ("water-fearing") or nonpolar end.

• It is the shape and amphipathic nature of the lipid molecules that

cause them to form bilayers spontaneously in aqueous

environments.

• Hydrophilic molecules dissolve readily in water because they contain

charged groups or uncharged polar groups that can form either

favorable electrostatic interactions or hydrogen bonds with water

molecules.

• Hydrophobic molecules, by contrast, are insoluble in water because

all, or almost all, of their atoms are uncharged and nonpolar and

therefore cannot form energetically favorable interactions with water

molecules.

• If dispersed in water, they force the adjacent water molecules

to reorganize into ice like cages that surround the

hydrophobic molecule.

• Because these cage structures are more ordered than the

surrounding water, their formation increases the free energy.

• This free energy cost is minimized, however, if the

hydrophobic molecules (or the hydrophobic portions of

amphipathic molecules) cluster together so that the smallest

number of water molecules is affected.

Membrane Lipids

• A typical biomembrane is assembled from

– Phosphoglycerides,

– Sphingolipids, and

– Steroids.

PHOSPHOLIPID BILAYERS

One structure that can result when phospholipids are suspended in

water is shown below. A bilayer of phospholipids forms a sphere in

which water is trapped inside. The hydrophilic phosphate regions

interact with the water inside and outside of the sphere. The fatty acids

of the phospholipids interact and form a hydrophobic center of the

bilayer.

• Phosphoglycerides, the most abundant class of lipids in

most membranes, are derivatives of glycerol 3-phosphate

• A typical phosphoglyceride molecule consists of a

hydrophobic tail composed of

– two fatty acyl chains esterified to the two hydroxyl groups in

glycerol phosphate and

– a polar head group attached to the phosphate group.

• The two fatty acyl chains may differ in the number of carbons

that they contain (commonly 16 or 18) and their degree of

saturation (0, 1, or 2 double bonds).

• Classified according to the nature of its head group.

• In phosphatidylcholines, the most abundant phospholipids in the

plasma membrane, the head group consists of choline, a positively

charged alcohol, esterified to the negatively charged phosphate.

• In other phosphoglycerides, an OH-containing molecule such as

ethanolamine, serine, and the sugar derivative inositol is linked to

the phosphate group.

• The plasmalogens are a group of phosphoglycerides that contain

one fatty acyl chain, attached to glycerol by an ester linkage, and

one long hydrocarbon chain, attached to glycerol by an ether linkage

(COOOC).

• These molecules constitute about 20 percent of the total

phosphoglyceride content in humans. Their abundance varies

among tissues and species but is especially high in human brain

and heart tissue.

Classification of Phosphoglycerides

Membrane Lipids

Membrane lipids

1. Phospholipids

Deformable (locomotion, cell division)

Facilitate fusion or splitting of

membranes

• The parts of a phospholipid molecule –

phosphatidylcholine

• A small tear in the bilayer creates a free edge with water; because

this is energetically unfavorable, the lipids spontaneously rearrange

to eliminate the free edge. (In eukaryotic plasma membranes, larger

tears are repaired by the fusion of intracellular vesicles.)

• The prohibition against free edges has a profound consequence: the

only way for a bilayer to avoid having edges is by closing in on itself

and forming a sealed compartment.

• This remarkable behavior, fundamental to the creation of a living

cell, follows directly from the shape and amphipathic nature of the

phospholipid molecule.

Phospholipid motility (The types of

movements possible for phospholipid molecules

in lipid bilayer)

Fluidity of membrane

Sphingolipids

• Derived from sphingosine, an amino alcohol with a long

hydrocarbon chain, and contain a long-chain fatty acid attached to

the sphingosine amino group.

• In sphingomyelin, the most abundant sphingolipid, phosphocholine

is attached to the terminal hydroxyl group of sphingosine.

• Thus sphingomyelin is a phospholipid, and its overall structure is

quite similar to that of phosphatidylcholine.

• Other sphingolipids are amphipathic glycolipids whose polar head

groups are sugars.

• Glucosylcerebroside, the simplest glycosphingolipid, contains a

single glucose unit attached to sphingosine.

• In the complex glycosphingolipids called gangliosides, one or two

branched sugar chains containing sialic acid groups are attached to

sphingosine.

• Glycolipids constitute 2–10 percent of the total lipid in plasma

membranes; they are most abundant in nervous tissue.

Cholesterol

• Cholesterol and its derivatives constitute the third important

class of membrane lipids, the steroids.

• The basic structure of steroids is a four-ring hydrocarbon.

• Although cholesterol is almost entirely hydrocarbon in

composition, it is amphipathic because its hydroxyl group

can interact with water.

• Cholesterol is especially abundant in the plasma membranes

of mammalian cells but is absent from most prokaryotic cells.

Cholesterol

A) Formula B) Schematic drawing C) Space-filling model

Cholesterol in a lipid bilayer

a) In one layer of lipid bilayer

b) In lipid bilayer

(a)

(b)

• As much as 30–50 percent of the lipids in plant plasma

membranes consist of certain steroids unique to plants.

• At neutral pH, some phosphoglycerides (e.g.,

phosphatidylcholine and phosphatidyl ethanolamine) carry

no net electric charge, whereas others (e.g.,

phosphatidylinositol and phosphatidylserine) carry a single

net negative charge.

• Nonetheless, the polar head groups in all phospholipids can

pack together into the characteristic bilayer structure.

• Sphingomyelins are similar in shape to phosphoglycerides

and can form mixed bilayers with them.

• Cholesterol and other steroids are too hydrophobic to form a

bilayer structure unless they are mixed with phospholipids.

Three classes of membrane lipids

Four major phospholipids in mammalian plasma membranes. Different head

groups are attached with the phosphate head in the lipid bilayer

The asymmetrical distribution of phospholipids and glycolipids in the

lipid bilayer of human red blood cells.

Membranes are Asymmetric

Lateral Asymmetry of Lipids:

Lipids can cluster in the plane of the membrane - they are not

uniformly distributed

Transverse asymmetry of lipids

In most cell membranes, the composition of the outer monolayer is

quite different from that of the inner monolayer

Lipid Composition Influences the

Physical Properties of Membranes

A typical cell contains myriad types of membranes, each with

unique properties bestowed by its particular mix of lipids and

proteins.

Several phenomena contribute to these differences.

For instance, differences between membranes in the endoplasmic

reticulum (ER) and the Golgi are largely explained by the fact that

phospholipids are synthesized in the ER, whereas

sphingolipids are synthesized in the Golgi.

The proportion of sphingomyelin as a percentage of total membrane lipid

phosphorus is about six times as high in Golgi membranes as it is in ER

membranes.

In other cases, the translocation of membranes from one cellular

compartment to another can selectively enrich membranes in

certain lipids.

Differences in lipid composition may also correspond to

specialization of membrane function.

For example, the plasma membrane of absorptive epithelial

cells lining the intestine exhibits two distinct regions:

apical surface faces the lumen of the gut and is exposed to widely

varying external conditions;

basolateral surface interacts with other epithelial cells and with

underlying extracellular structures.

In these polarized cells, the ratio of sphingolipid to

phosphoglyceride to cholesterol in the basolateral membrane

is 0.5:1.5:1, roughly equivalent to that in the plasma

membrane of a typical unpolarized cell subjected to mild

stress.

In contrast, the apical membrane of intestinal cells, which is

subjected to considerable stress, exhibits a 1:1:1 ratio of

these lipids.

The relatively high concentration of sphingolipid in this

membrane may increase its stability

Membranes contain

specialized lipids and

proteins

Proteins 30-70% Phospholipids 7-40% Sterols 0-25% Specialized membranes

More than 90% Rhodopsin in

photoreceptor disc membrane

Protein rich mitochondrial

membranes

Transport optimized Red Blood Cell

membrane