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CHAPTER 3
The Cellular Level of Organization
INTRODUCTION
• A cell = basic living, structural, & functional unit of body
• Cytology = study of cell structure
• Cell physiology = study of cell function
• Generalized view of cell = composite of many different
cells
• No single cell includes all of the features seen
in the generalized cell.
PARTS of a CELL
• Cell can be divided into three principal parts:
– Plasma (cell) membrane (PM)
– Cytoplasm
• Cytosol
• Organelles (except for the nucleus)
– Nucleus
THE PLASMA MEMBRANE
• Flexible, sturdy barrier surrounding cytoplasm of cell
• Fluid mosaic model (Figure 3.2)
– “Proteins in a sea of lipids”
– Lipid bilayer (amphipathic)
• two back-to-back layers of PL molecules
– FA tail region = NONpolar (hydrophobic)
– PO4-3 head region = polar (hydrophilic)
• cholesterol
• glycolipids
– glyco = “sugar”
– extracellular face only
Arrangement of Membrane Proteins
• Integral proteins
– amphipathic
– anchored w/in membrane
• Peripheral proteins
– associated w/ head of PL or w/ integral protein
– can be removed from membrane
– glycoproteins
• CHO groups protrude into ECF
• glycocalyx
Functions of Membrane Proteins
• Ion channels (integral)
• Transporters (integral
• Receptors (integral)
• Enzymes (integral or peripheral)
• Cell identity marker (glycoprotein)
• Linkers (integral and peripheral)
Membrane Fluidity
• “Mobility with structure”
– movement w/in bilayer
– no flip-flop
• Dependent upon:
– # of double bonds in fatty acid tails of lipids
– amount of cholesterol present
• stabilizes membrane
• reduces fluidity @ normal body temp.
• Allows self-repair of lipid bilayer
• Enables many cellular processes
– assembly of membrane proteins
– cell movement, growth, etc.
Membrane Permeability
• Selective permeability
– Permeable to small, nonpolar, uncharged molecules
– Permeable to water
– Impermeable to ions & charged or polar molecules
• Increased by transmembrane proteins
• Macromolecules must cross PM via vesicular transport.
Gradients Across PM
• Difference in concentration of a chemical or electrical
charge between opposite sides of PM
– Concentration gradient
– Electrical gradient
– Electrochemical gradient
• Allow for movement of substances across PM
– “downhill” movement
• Oxygen & Na+ more concentrated outside cell
• CO2 & K+ more concentrated inside cell
TRANSPORT ACROSS PM
• “Downhill” movement is passive
– Diffusion thru lipid bilayer
– Diffusion thru ion channels
– Facilitated diffusion
• Requires transporter (usually a protein)
• “Uphill” movement is “active”
– Requires cellular energy in form of ATP
• Substances can also enter or leave cell thru vesicle
transport
Principles of Diffusion
• Diffusion = random mixing of particles that occurs in a
solution as a result of the kinetic energy of the particles
• Occurs down concentration gradient
• Equilibrium eventually achieved
• Diffusion rate influenced by :
– Steepness of the concentration gradient
– Temperature
– Size or mass of the diffusing substance
– Surface area
– Diffusion distance
Diffusion Through Lipid Bilayer
• Nonpolar, hydrophobic molecules diffuse freely
– respiratory gases
– lipids
– small alcohols
– ammonia
• Important for gas exchange, absorption of some
nutrients, & excretion of some wastes
Diffusion Thru Membrane Channels
• Most are ion channels
– small, inorganic (hydrophilic) ions
• Ion channels are selective
– gated or open all the time
– slower than free diffusion because site
specific
Osmosis
• Water molecules penetrate membrane via diffusion
– through lipid bilayer
– through aquaporins
• transmembrane proteins that function as water
channels
• Water moves from an area of lower solute
concentration to an area of higher solute concentration.
• Occurs only when membrane is permeable to
water but not to certain solutes
Osmotic Pressure
• Force exerted on membrane by
impermeable solute
• Proportional to [solute] that cannot cross
membrane
Tonicity
• Measure of solution’s ability to change volume of cells
by altering their water concentration
• Isotonic solution
– [solute] is same on both sides of PM
– RBCs maintain normal shape (Fig. 3.7a)
• Hypotonic solution
– [solute] in sol’n lower than inside cell (cytosol)
– Water flows into cell to equalize [solute]
– RBCs undergo hemolysis (Fig. 3.7b)
• Hypertonic solution
– [solute] in sol’n higher than inside cell (cytosol)
– Water flows out of cell to equalize [solute]
– RBCs undergo crenation (Fig. 3.7c)
Facilitated Diffusion
• Transport of highly charged or polar solutes across PM
• Solute binds to specific transporter
– Transporter undergoes a conformational change
– Solute carried from one side of PM to other
• Saturable process
– Transport maximum
– Rate of facilitated diffusion dependent upon:
• steepness of concentration gradient
• # of transporter proteins available
• Transport of glucose, urea, fructose, galactose, & some
vitamins
• **PASSIVE process!!
Facilitated Diffusion of Glucose
• Glucose binds transport protein
• Transport protein Δ shape
• Glc moves across PM (down
concentration gradient)
• Kinase enzyme reduces
[glc] inside cell
– glc-6-P unusable by cell
• Transporter proteins always
bring glucose into cell
Active Transport
• Moves solutes AGAINST concentration gradient
• Requires energy
– ATP (primary)
– Ion concentration gradient
(secondary)
• Saturable process
• Ex: Na+/K+ pump (Fig 3.8)
Primary Active Transport
• Na+/K+ pump most prevalent (Figure 3.8)
– Energy derived from ATP hydrolysis
– Maintains low [Na+] and high [K+] in cytosol
• 3 Na+ bind transporter (intracellular side of
PM)
• ATP hydrolysis causes conformational
change & release of Na+ to ECF
• 2 K+ bind & cause release of Pi to cytosol
• Conformational change & 2 K+ released in
cytosol
Secondary Active Transport
• Energy stored in Na+ or H+ concentration gradient
drives other substances against own gradients
• Indirect use of ATP
• Digitalis slows Na+/Ca+2 ion antiporters
– allows more Ca+2 to stay inside heart muscle
cells
• increases force of contraction 
strengthens heartbeat
Transport in Vesicles
• Invaginations of PM enclose substances &
transport into or out of cell
– Endocytosis = bringing something into cell
– Exocytosis = release of something from cell
• Vesicular transport is an active process
Vesicular Transport--Endocytosis
• Receptor-mediated endocytosis = selective uptake
of large molecules/particles by cells
– Ex: internalization of LDL particles
• Phagocytosis = macrophages & neutrophils engulf
large particles
– Particle binds to receptor protein on PM & is
surrounded by pseudopods
– Disposal of microbes, old cells, etc.
• Pinocytosis (bulk-phase endocytosis) = cell drinking
– No receptor proteins
Vesicular Transport--Exocytosis
• Exocytosis
– Vesicle formation inside cell
– Vesicle fuses w/ cell membrane
– Vesicle products released from cell
• digestive enzymes, hormones, NT, wastes
– Replace/recycle cell membrane lost during
endocytosis
CYTOPLASM
• Cytosol = the semifluid portion of cytoplasm that contains
inclusions and dissolved solutes
• Organelles = specialized structures that perform specific
functions in cellular growth, maintenance, and repro.
The Cytoskeleton
• Network of protein filaments
throughout cytoplasm
• Functions:
– Structural framework of
cell
– Cell/organelle movement
• Microfilaments
• Intermediate filaments
• Microtubules
Centrosomes
• Contain centrioles: paired
cylinders arranged at right
angles to one another
• Organize microtubules in
interphase cells
• Organize mitotic spindle
during cell division
Cilia and Flagella
• Hair-like structures important
for cellular movement
• Cilia
– numerous, short,
projections extending from
cell surface
– move materials across
surface of cell
• Flagella
– much longer than cilia
– usually move an entire cell
Ribosomes
• Composed of ribosomal RNA & protein
• Sites of protein synthesis
• Free ribosomes are loose in cytosol
– synthesize proteins found inside the cell
• Membrane-bound ribosomes
– attached to endoplasmic reticulum or nuclear
membrane
– synthesize proteins needed for plasma membrane or
for export
• Inside mitochondria, ribosomes synthesize mitochondrial
proteins
Ribosomal Subunits
• Large + small subunits
– made in the nucleolus
– assembled in cytoplasm
Endoplasmic Reticulum (ER)
• Network of membranes that form flattened
sacs
• Store, package & transport newly synthesized
molecules
• Detoxification (SER in liver)
• Releases Ca+2 ions in muscle contraction
(sarcoplasmic reticulum)
• Fatty acid & steroid synthesis (liver SER)
Endoplasmic Reticulum
• Rough ER (RER)
– Extension of nuclear membrane
– Ribosomes on outer surface
– Secretory, membrane & organelle proteins
• Smooth ER (SER)
– Extension of rough ER
– No ribosomes
– Detox, FA/steroid synth., Ca release in muscle
Golgi Complex
• Flattened membranous sacs that process, sort, and
deliver proteins & lipids to other parts of cell
• Different enzymes allow for modification/packaging of
various proteins
Lysosomes
• Membrane-enclosed vesicles formed from Golgi
• Numerous digestive enzymes
• Functions
– digest foreign substances
– autophagy
• recycles own organelles
– autolysis
• tissue damage after death
• Tay-Sachs disease
– caused by absence of single lysosomal enzyme
– glycolipids accumulate & interfere w/ nerve function
Peroxisomes
• Similar in structure to, but smaller than lysosomes
• Contain oxygen-requiring enzymes
– Oxidases  oxidize various organic compounds
– Catalases  break down H2O2
• Important in normal catabolism of amino acids and fatty
acids
• Oxidize toxic substances
– Alcohols
– Formaldehyde
Proteosomes
• Destroy unneeded, damaged, or faulty proteins
• Proteases cut proteins into small peptides
• Faulty proteosomes are possible factor in some
degenerative diseases
– Fail to break down abnormal proteins
– Parkinson’s & Alzheimers
Mitochondria
• Cellular powerhouses
– Site of ATP production
• Catabolism of nutrients
• O2 required  aerobic
– Located where O2 enters cell or
ATP is used
• Bound by double membrane
• Cristae
– Folds in inner membrane
– Enormous surface area for
reactions of cellular respiration
• Matrix
– Central cavity
– Site of metabolic reactions
NUCLEUS
• Directs cellular activity
• Controls cell structure
• Most body cells have one nucleus (mononucleate)
– RBCs are anucleate
– Skeletal muscle fibers are multinucleate
• Parts of nucleus include
– nuclear envelope which is perforated by nuclear pores
– nucleolus
– genetic material (DNA)
• Contains cell’s hereditary units (genes) which are
arranged on chromosomes
NUCLEUS
• 46 (23 pair) human chromosomes
– Genes found on chromosomes
– Genes direct synthesis of specific protein
• Non-dividing cells contain nuclear chromatin
– Loosely packed DNA, RNA & protein complex
– Histones = proteins that direct DNA folding
• Dividing cells contain chromosomes
– Tightly packed DNA
– DNA copied itself before condensing into chromatids
Chromosomes
• Each chromosome = long
molecule of DNA coiled
together with several
proteins
• Human somatic cells have
46 chromosomes (23 pairs)
• Various levels of DNA
packing represented by
nucleosomes, chromatin
fibers, loops, chromatids, &
chromosomes
PROTEIN SYNTHESIS
• Genes expressed as proteins
• Proteins determine phys/chem characteristics of cells
• DNA is template for protein synthesis
• Transcription (txp)
– Genetic info in DNA copied onto single-stranded RNA
• Three types of RNA
– Messenger RNA (mRNA)
– Ribosomal RNA (rRNA)
– Transfer RNA (tRNA)
• Translation
– mRNA read by ribosomes
– “Message” translated into a. a. sequence of protein
Transcription
• DNA sense strand = template for creation of mRNA strand
• RNA polymerase (RNApol) attaches to promoter sequence
& initiates txp
• RNApol reaches terminator sequence & detaches  txp
stops
• Genes contain XS information
– Pre-mRNA contains introns that are cut out by enzymes
– Exons: regions of mRNA code for segments of protein
• “gene splicing”
• snRNPs
– Thus 1 gene can yield several proteins
Protein Synthesis
• Instructions for making specific proteins found in DNA (your
genes)
– transcribe that information onto
mRNA molecule
• each sequence of 3 nucleotides in DNA = base triplet
• each triplet transcribed as 3 RNA nucleotides (codon)
– translate “message” into sequence of amino acids in order
to build protein
• each codon must be matched by anticodon found on
the tRNA carrying a specific amino acid
Translation
• Sequence of nucleotides (ntd) on mRNA is “read” by rRNA
to construct a protein
• Small ribosomal subunit is attachment site for mRNA
• Large ribosomal subunit has 2 tRNA binding sites
– P site: where tRNA-a.a. attaches to mRNA
– A site: holds incoming tRNA-a.a.
• Specific tRNA molecules carry specific amino acids
• 3-nucleotide sequences = codons
– AUG is ALWAYS the start codon
– tRNA anticodon = UAC & it codes for methionine
• Anticodons on tRNA match specific codons on mRNA so
proper a.a can be strung together to create protein
Translation
Sequence is as follows:
• Initiator tRNA
• Start codon on mRNA
• Functional ribosome formed
– initiator tRNA fits into P site on rRNA
• Anticodon of tRNA match codons of mRNA
• Stop codon on mRNA
CELL DIVISION
• Process by which cells reproduce themselves
– nuclear division (mitosis and meiosis)
– cytoplasmic division (cytokinesis)
• Somatic cell division: reproduction of any body cell
except sex cells
– nuclear division (mitosis)
– cytokinesis
– distribute two sets of chromosomes—one set into
each of two separate nuclei
• Reproductive cell division: production of gametes
– nuclear division (meiosis)
– cytokinesis
Chromosome Number
• Human somatic cells contain 46 chromosomes (23
pairs)
• Homologous chromosomes (homologs) = two
chromosomes that make up a chromosome pair
• A cell with a full set of chromosomes is diploid (2N)
• A cell with only one chromosome from each pair is
haploid (N)
– Mitosis yields diploid cells
– Meiosis yields haploid cells
Cell Cycle in Somatic Cells
• Orderly sequence of events by which cell duplicates its
contents and divides in two
• Consists of interphase and mitotic phase (Figure 3.28)
Interphase
• Cell carries on every life process except division
• Doubling of DNA and centrosome
• Three subphases of interphase:
– G1 = replication of cytosolic components (G0 if
non-dividing cell)
– S = replication of chromosomes
• “commitment” stage cell will divide
– G2 = cytoplasmic growth
Replication of Chromosomes During Interphase
• Doubling of genetic material
during interphase (S phase)
• DNA molecules unzip (histones)
• Mirror copy formed along each
old strand
• Nitrogenous bases pair with
complementary base
• 2 complete, identical DNA
molecules formed
Interphase
• Cell shows distinct nucleus
• DNA present as chromatin
• Nuclear membrane in tact
MITOSIS: Prophase
• Chromatin condenses & shortens into chromosomes
– Identical chromatids joined by centromere
• Centrosomes migrate to opposite poles
• Disintegration of nuclear membrane/nucleolus
MITOSIS: Metaphase
• Centromeres line up at exact center of mitotic spindle,
(metaphase plate or equator)
MITOSIS: Anaphase
• Splitting & separation of centromeres
• Chromatids from each pair move toward opposite poles of cell
– appear V-shaped as they are pulled by centromeres
• Late anaphase: formation of cleavage furrow begins
MITOSIS: Telophase
•
•
•
•
Begins when chromatid movement stops
Chromosomes at opposite poles revert to chromatin form
New nuclear envelope/nucleoli form
Mitotic spindle breaks up
CYTOPLASMIC DIVISION: Cytokinesis
• Division of parent cell’s
cytoplasm and organelles
• Begins late anaphase/
early telophase
• Following completion of
cytokinesis, interphase
begins
• Cancer = uncontrolled cell
division  some
anticancer drugs stop this
by inhibiting spindle
formation
Control of Cell Destiny
• Three possible destinies of a cell
– Live & function without dividing
– Growth & division
– Death
• CDKs crucial for regulation of cell growth/division
– Regulated by cyclins
• Apoptosis = programmed cell death
– Triggered intra- or extracellularly by “cell-suicide” gene
– Removes unneeded/unwanted cells
• Necrosis = pathological (abnormal) cell death
– Stimulates inflammatory response
• Tumor-suppressor genes normally inhibit cell division
– Ex: p53 arrests cells in G1  damage leads to breast or
colon cancers
Reproductive Cell Division: Meiosis
• Results in production of haploid (n) cells
containing only 23 chromosomes
• Occurs in two successive stages:
– Meiosis I
– Meiosis II
CELLS AND AGING
• Aging = normal, progressive alteration of body’s
homeostatic adaptive responses
• Physiological signs of aging:
– Gradual deterioration in function
– Decline in responsiveness
– Net decrease in number of cells in body & increased
dysfunction of remaining cells
• Extracellular components of tissues (e.g., collagen fibers
and elastin) also change with age
• Theories of aging:
– genetically programmed cessation of cell division, glc
addition to proteins, free radical rxn, & excessive immune
responses
DISORDERS: HOMEOSTATIC IMBALANCES
• Cancer = group of diseases characterized by
uncontrolled cell proliferation
• Cells that divide without control develop into a tumor or
neoplasm.
• Cancerous neoplasm = malignant tumor or malignancy
– Capable of metastasizing
• spread of cancerous cells to other parts of the
body
• A benign tumor = noncancerous growth
Cancer = Uncontrolled cell division
•
Hyperplasia = increased number of cell divisions
– benign tumor does not metastasize (spread)
– malignant tumors spread because detach from tumor &
enter blood/lymph
• Causes
– exposure to carcinogens, x-rays, viruses
– every cell has genes that regulate growth & development
– mutations in those genes due to radiation or chemical
agents causes excess production of growth factors
•
• Carcinogenesis
– multistep process that takes years (and requires many
different mutations) to occur
Types of Cancer
• Carcinomas arise from epithelial cells.
• Melanomas = cancerous growths of melanocytes
• Sarcomas arise from muscle cells or connective
tissues.
• Leukemia = cancer of blood-forming organs
• Lymphoma = cancer of lymphatic tissue
Growth and Spread of Cancer
• Cancer cells divide rapidly and continuously.
– Trigger angiogenesis
• Metastasis occurs when cancer cells leave site of origin
& travel to other tissues/organs
Causes of Cancer
• Normal counterparts of oncogenes = proto-oncogenes
– found in every cell
– cells fcn normally until a malignant Δ occurs
• Anti-oncogenes or tumor-suppressing genes
– may produce proteins that normally oppose the
action of an oncogene or inhibit cell division
• Carcinogenesis = multistep process involving mutation
of oncogenes & anti-oncogenes
– 10 distinct mutations may have to accumulate in a
cell before it becomes cancerous
Treatment of Cancer
• Difficult because it is not a single disease & because all
cells in a tumor do not behave in same way
• Various treatments include
– Surgery
– Chemotherapy
– Radiation therapy