G.R. Pitts, Ph.D, J.R. Schiller, Ph.D. & James F. Thompson, Ph.D.

• The Cell is the fundamental structural and functional unit of living organisms
• The activity of an organism is dependent on both the individual and collective activities of its cells
• Cell actions are determined and made possible by specific subcellular structures – The Principle of
Complementarity
• Cells come from cells

• Overview
– The cell is the unit of life: it contains everything needed to survive
– Loss of cellular homeostasis → disease
– Made of complex organic molecules (containing mostly carbon, hydrogen, oxygen, nitrogen and traces of others elements)
– Organized into multiple structures called organelles
– Many different shapes and sizes
20 µm - 1+ m
5-24 µm

3 basic parts
1. Nucleus
2. Cytoplasm
• all cellular contents between plasma membrane and nucleus
• organelles are specialized internal structures
3. Plasma membrane
Not all cells contain every structure.

• Fluid: a dynamic “fluid” bilayer in which molecules can move past each other within the membrane
• Mosaic: a mix of molecular components
– Lipids: phospholipid bilayer foundation with some cholesterol mixed in
– Proteins: diverse, can be varied and regulated to alter membrane functions
– Carbohydrates: combined with lipids/proteins make up the glycocalyx
• “sticky” surface that functions in cell recognition
– Individual molecules are recycled often
• The kinds and numbers of membrane molecules, especially proteins, determine membrane function.

• 50-50 ratio by weight: lipid/protein
• Far more lipid molecules than protein molecules because of protein molecules’ larger sizes

• Phospholipids 75%
– Bilayer
– Phosphate heads are polar, thus hydrophilic, point out towards interstitial fluid and in toward cytoplasm
– Non polar fatty acid tails are hydrophobic, make up middle of membrane
• Glycolipids 5%
– Contribute to glycocalyx
• Cholesterol 20%
– Increases mobility (fluidity”) of phospholipids

• Determine the functions a cell can perform
• Composition varies widely among cell types
– Integral proteins – located within the membrane
• channels
• transporters
• receptors
• intracellular junctions
• enzymes
• cytoskeleton anchors
• cell identity markers (glycoproteins)
Transport Cell Joining
Enzyme Cell Recognition
– Peripheral proteins – located on either face of the membrane
• A similar list of many functions, with the exceptions of transporters and channels
Anchor Receptor

• Communication with other cells and tissues
• Selective permeability - allows passage of some substances; limits others
– dependent on:
• molecular size
• lipid solubility
• charge
– membranes impermeable to all charged molecules
– Ions only move through a membrane through channels
• the presence of channels & transporters is very specific

Tight Junctions:
Impermeable junctions that encircle adjacent cells.
Desmosones:
Anchoring junctions between cells.
Gap Junctions:
Communicating junctions that allow substance to pass from one cell to another.

• Mechanisms which move materials across cell and organelle membranes without expending cellular energy
• Examples:
– Simple Diffusion
– Diffusion across a cell membrane
– Facilitated Diffusion

• Moves materials across cell and organelle membranes without expending cellular energy
• Simple Diffusion
– kinetic energy is everywhere - allows mixing or diffusion
– diffusion requires a concentration gradient
• high concentration in one area, lower concentration in another
• if areas are continuous (connected), particles move with (down) the concentration gradient
• eventually it reaches equal concentration everywhere - equilibrium equilibrium

• Diffusion through the plasma membrane
– selective permeability
– water and lipid-soluble molecules move freely through the membrane
– small non-lipid-soluble substances may move through specific channels

1. Increased temperature increases diffusion rate
2. Greater concentration gradients increase diffusion rate
3. Larger surface area increases diffusion rate
4. Smaller particle sizes increase diffusion rate
5. Time - diffusion decreases as concentrations equalize

• The diffusion of water from an area of higher [H
2
O] to lower [H
2
O]
• Water concentration = 1/solute concentration
• Polar water molecules move through aquaporin channels (AQP)
• Or (perhaps) “wiggle” through phospholipids

• Osmolarity: the total concentration of all solutes
• Osmotic pressure (σ) – the net pressure effect of individual particles in solution
• Hydrostatic pressure (h) = fluid pressure is created by osmosis h
H
2
0 diffuses
σ

• The ability of a solution to change the shape (“tone”) of cells by altering their internal water volume
• Isotonic solutions
– Solute concentration is the same inside and outside the cells
– No net diffusion of water
(e.g., “normal” saline solution is isotonic to blood plasma)
Isotonic

• Hypertonic solution
 a solution with higher [solute] than inside cells
 water moves out of cells & cells shrink (crenation)
• Hypotonic solution
 a solution with lower [solute] than inside cells
 water moves into cells, cells swell & may rupture isotonic hypertonic hypotonic

• Integral proteins allow larger molecules or charged/polar ions to diffuse across membrane
• Passive transport: because substances diffuse down the concentration gradient; no cellular energy (ATP) is required
• May be regulated by hormones example: insulin will increase cellular glucose uptake
Some substances need help crossing the membrane
Carrier Channel

• Some substances cannot move passively because they:
– are too big
– have the wrong charge
– must be moved against their concentration gradient
• Energy must be expended for active processes (they require the energy derived from splitting ATP = energy of hydrolysis)
• Two different mechanisms:
1. active transport (primary and secondary)
2. vesicular transport

• Integral membrane proteins (“pumps” or
“transporters”) use ATP hydrolysis energy to move substances against their concentration gradient
• Primary active transport: pumps use ATP energy to transport substances directly across the membrane.
– many substances are moved by primary active transport: Na + , K + , H + , Ca ++ , I , Cl , amino acids, monosaccharides, etc.

• pumps use ATP hydrolysis energy
directly to move substances
See also Fig. 3.11, p. 75.
– ATP is hydrolyzed to move specific ions
– without ATP energy, the pump does not work
• Na + / K + ATPase
– pumps 3 Na + out / 2 K + in during each cycle
– because Na + & K + ions always leaks across the membrane, the pump must always operate sodium-potassium pump

• Secondary active transport (facilitated transport): a primary transporter use ATP energy to create a concentration gradient of one substance; that gradient will drive a nearby facilitated transporter to move a second substance
 two types of secondary active transport
– Symport/Symporter – transports two substances in the same direction (co-transport)
– Antiport/Antiporter – transports two substances in opposite directions (countertransport)

• ATP energy is used
indirectly to move substances
• ATP energy drives an ion pump to create a concentration gradient; then a carrier protein uses the energy of the concentration gradient to
“drag” or “push” transport of another substance(s) by facilitated transport
A Na
+ ion and a glucose bind to the symport, then the symport transports the glucose and
Na + ion inside the cell.

• Generating/maintaining a resting membrane potential
– all cells are polarized
• negatively charged inside
• positively charged outside
– Na + /K + ATPase creates the unequal charge distribution
• Na + tends to diffuse inside on its own via leaky channels
• even more K + tends to diffuse outside on its own via leaky channels
• the sodium-potassium pump transports 3 Na + ions out & 2 K + ions in with each cycle, using the energy from one ATP hydrolysis
• more negatively charged proteins (A ) are located within the cell
• These disequilibria in ions create the charge differential
– Electrochemical gradient
• the net effect of all charged ions on either side of the membrane

• The transfer of large molecules and fluids across membranes via vesicles. This type of transport mechanism includes exocytosis and
endocytosis.

Phagocytosis
Clathrin-mediated endocytosis Receptor-mediated endocytosis

• Membrane Receptors: detect cell markers and chemical signals
– contact /identity signaling – membrane marker proteins identity cells as to type or function
• ABO and Rh blood types
• HLA antigens on other tissues
– contact inhibition - regulates cell proliferation
– electrical signaling - channels responding to voltage changes
(changes in the concentrations of charged ions)
– chemical signaling – various signal compounds: neurotransmitters, hormones, local hormones, and other ligands

1. Cell adhesion molecules (CAMs):
A. Act as anchors, attaching cells to their environment
B. Act as arms for cell movement
C. Stick into blood vessels to attract white blood cells to damaged cells or extracellular matrix
D. Form desmosomes, tight junctions, etc.

• Cytosol: viscous, semitransparent fluid in which other cytoplamic elements are suspended
• Cytoplasmic organelles you should know
– Mitochondria
– Ribosomes*
– Rough endoplasmic reticulum (Rough ER)
– Smooth endoplasmic reticulum (Smooth ER)
– Golgi apparatus
– Lysosomes & Peroxisomes
– Cytoskeleton*
– Nucleus
– Nucleoli*
[* not membrane-bound]
• Inclusion bodies: substances
– Centrioles*
– Cilia
– Flagella not enclosed in membrane

• Cell’s control center
• Usually visible
• Nuclear envelope
– double membrane
– nuclear pores in membrane allow passage of substances between cytoplasm and nucleus
• Contains the hereditary material (DNA)
– DNA carries instructions for making proteins
– determines cell structure, coordinates activities of the cell

• Nucleoli
– darker staining, oval/spherical bodies within the nucleus
– clusters of DNA, RNA, and protein (not membranebound)
– the site of ribosomal RNA synthesis and ribosomal subunit assembly

• grainy threadlike material seen in the nucleus
• DNA molecules organize into large, compact visible chromosomes before each cell division
• chromosomes contain DNA & coiling proteins
• DNA is first wrapped around histone proteins -
"beads on a string”
• then higher levels of DNA packaging
(supercoiling)

Histone proteins form the nucleosome core

• Interphase
– normal cell growth
– three subphases
• G
1
– growth and metabolism
– protein replication
• S (“synthesis” of DNA)
– preparation for division
– DNA replication
• G
2
– more metabolism
– further preparation
– enzymes, proteins for mitosis
• Mitosis = nuclear division

P
• Prophase
M
• Metaphase
• Anaphase
• Telophase
A
T

• semi-conservative
• helicase – unwinds DNA
• DNA polymerase
– one strand is the template
– builds a complementary strand
– bases pair with hydrogen bonds
• A-T
• C-G

• Transcription (in nucleus)
– Transcription of DNA into mRNA
– DNA – genetic blue print
– template
– triplet code - 3 bases/AA
– exons - expressed
– introns – excised
– mRNA – messenger RNA
• Translation (in cytoplasm)
• mRNA triplet codons are read to build primary protein structure
– Ribosome
• active site for enzymes to form peptide bonds

• DNA contains a sequence of nitrogenous bases which codes for the sequence of amino acids in a protein
– A triplet code, in which each codon is composed of 3 bases, forms the “genetic code”
• During transcription
– one strand of DNA serves as a template for formation of messenger RNA
– mRNA has bases complementary to the base series in the
DNA
• Messenger RNA is processed, with intron removal, before leaving the nucleus

• mRNA carries the codon sequence to the ribosomes
(rRNA and protein) in the cytoplasm
• each tRNA carries a particular kind of amino acid
– each tRNA also carries a 3-base anticodon which pairs complementarily to a codon of the mRNA
• during translation
– the linear sequence of codons in the mRNA determines the order of tRNAs and their attached amino acids
– sequential peptide bond formation produces the primary structure of the protein at the ribosome

Note: You will find additional slides after this “end” slide with additional details of cell organelles and processes, which you may review on your own.

Animal Physiology, Hill et al., 2004

• A chemical signaling mechanism
• Ligand binds to receptor
• Receptor activates “G protein” that activates an enzyme
• The enzyme activates a second messenger
• Second messenger activates other enzymes

• The powerhouse of the cell
– Generates most ATP
• Have 2 membranes
• Contain mitochondrial DNA
(passed from mother only)
• Arose from bacterial infection

• Interconnected tubes & parallel membranes enclosing cisternae
• Rough ER
– Studded with ribosomes
– Manufactures secreted proteins
– Manufactures integral proteins and phospholipids

• Does not contain ribosomes
• Not involved in protein synthesis
• Catalyzes chemical reactions
– Lipid metabolism
– Steroid synthesis
– Absorption, synthesis, and transport of fats
– Drug detoxification
– Breakdown of glycogen
– Ca 2+ ion storage

• The protein traffic director
• Modifies and packages proteins and lipids made in the RER
• Produces lysosomes and secretory vesicles/granules

• Spherical vesicles containing digestive enzymes in acidic conditions
– Implicated in aging
• Enzymes digest:
– bacteria, viruses, toxins
– non-functional organelles
– non-useful tissues
– bone

• Vesicle bound redox enzymes
• Detoxify alcohols and formaldehyde
• Neutralize free radicals (unstable molecules with unpaired electrons)
• Carry out other oxidation-reduction reactions

• Microtubules
– Large diameter, hollow tubes made of tubulins
– Extend outward from the centrosome
– Anchor and transport organelles
– Very dynamic

• Intermediate filaments
– Medium sized filament
– Act as “guy wires”

• Microfilaments
– The smallest filament
– Composed of actin
– Involved in cell motility and cell shape
– Responsible for muscle contraction when actin interacts with myosin

• Centrosome
– Microtubule organizing center
– Contains centrioles
• Centrioles
– Involved in mitosis
– Give rise to cilia and flagella

Unwinding of DNA by helicase
Replication fork
Replication bubble

Note: End of additional review slides.