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: MeiosisReproductive 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