Chapter 3

Cells: The Living Units

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

The Cell Theory

• 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

The Cellular Basis of Life• 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 sizes5-24 µm

20 µm - 1+ m

General Cell Structure3 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.

Plasma Membrane Structure: Fluid Mosaic Model

• 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.

Plasma Membrane Structure• 50-50 ratio by weight: lipid/protein• Far more lipid molecules than protein molecules because of

protein molecules’ larger sizes

Plasma Membrane Lipids• 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

Plasma Membrane Proteins• 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)

– Peripheral proteins – located on either face of the membrane

• A similar list of many functions, with the exceptions of transporters and channels

Transport

Enzyme

Receptor Anchor

Cell Recognition

Cell Joining

Fluid Mosaic Model: Functions

• 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

Membrane JunctionsTight 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.

Passive Transport

• Mechanisms which move materials across cell and organelle membranes without expending cellular energy

• Examples:– Simple DiffusionSimple Diffusion– Diffusion Diffusion across a cell membrane– Facilitated DiffusionFacilitated Diffusion

Passive Transport• Moves materials across cell and organelle membranes

without expending cellular energy• Simple DiffusionSimple 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

Simple Diffusion

• 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

Factors Affecting Diffusion

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

Osmosis• The diffusion of water from an area

of higher [H2O] to lower [H2O]

• Water concentration = 1/solute concentration

• Polar water molecules move through aquaporin channels (AQP)

• Or (perhaps) “wiggle” through phospholipids

Osmolarity and Osmotic Pressure• 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

σH20 diffuses

Tonicity• 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

Tonicity• Hypertonic solution

a solution with higher [solute] than inside cells water moves out of cells & cells shrink (crenation)crenation)

• Hypotonic solution a solution with lower [solute] than inside cells water moves into cells, cells swell & may rupture

isotonic hypotonichypertonic

Facilitated Diffusion / Passive Transport

• 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 uptakeChannelCarrier

Some substances need help crossing the membrane

Active Transport Processes• 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

Active 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.

Primary Active Transport• pumps use ATP

hydrolysis energy directly to move substances– ATP is hydrolyzed to move

specific ions– without ATP energy, the

pumppump 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

See also Fig. 3.11, p. 75.

Secondary Active Transport

• 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/SymporterSymport/Symporter – transports two substances

in the same direction (co-transport)– Antiport/AntiporterAntiport/Antiporter – transports two substances

in opposite directions (countertransport)

Secondary Active Transport• 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.

Resting Membrane Potential• 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

Vesicular Transport• The transfer of large molecules and fluids across membranes via

vesicles. This type of transport mechanism includes exocytosis and endocytosis.

Endocytosis

Phagocytosis

Receptor-mediated endocytosis

Clathrin-mediated endocytosis

Cell-Environment Interactions

• Membrane Receptors: detect cell markers and chemical signals– contact /identity signalingcontact /identity signaling – membrane

marker proteins identity cells as to type or function

• ABO and Rh blood types• HLA antigens on other tissues

– contact inhibitioncontact inhibition - regulates cell proliferation

– electrical signalingelectrical signaling - channels responding to voltage changes (changes in the concentrations of charged ions)

– chemical signalingchemical signaling – various signal compounds: neurotransmitters, hormones, local hormones, and other ligands

Cell-Environment Interactions1. 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.

The Cytoplasm• 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*

• Inclusion bodies: substancesnot enclosed in membrane

– Centrioles*– Cilia– Flagella

[* not membrane-bound]

The Nucleus• 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

The Nucleolus• Nucleoli

– darker staining, oval/spherical bodies within the nucleus

– clusters of DNA, RNA, and protein (not membrane-bound)

– the site of ribosomal RNA synthesis and ribosomal subunit assembly

Chromatin• 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)

Chromatin Organization• DNA is packaged by

various levels of supercoiling

Chromatin Organization

Histone proteins formthe nucleosome core

The Cell Cycle• Interphase

– normal cell growth– three subphases

• G1

– growth and metabolism– protein replication

• S (“synthesis” of DNA)– preparation for division– DNA replication

• G2

– more metabolism– further preparation– enzymes, proteins for

mitosis

• Mitosis = nuclear division

Mitosis - Nuclear Division

• Prophase

• Metaphase

• Anaphase

• Telophase

PM

AT

DNA Replication: Summary• 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

Protein Synthesis• 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

Translation at the Ribosome

Gene Expression Review• 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

Gene Expression Review (cont.)

• 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

End Chapter 3

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

Electrochemical Equilibrium

Animal Physiology, Hill et al., 2004

Electrochemical Equilibrium

Normal Concentrations of Ion and Other Molecules

Chemical Signaling: G-Protein Linked Receptors

• 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

Mitochondria

• The powerhouse of the cell– Generates most ATP

• Have 2 membranes

• Contain mitochondrial DNA (passed from mother only)

• Arose from bacterial infection

Endoplasmic Reticulum• Interconnected tubes &

parallel membranes enclosing cisternae

• Rough ER– Studded with ribosomes

– Manufactures secreted proteins

– Manufactures integral proteins and phospholipids

Smooth Endoplasmic Reticulum• 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– Ca2+ ion storage

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

Endomembrane Transport

Lysosomes

• Spherical vesicles containing digestive enzymes in acidic conditions– Implicated in aging

• Enzymes digest:– bacteria, viruses, toxins– non-functional organelles– non-useful tissues– bone

Peroxisomes

• Vesicle bound redox enzymes

• Detoxify alcohols and formaldehyde

• Neutralize free radicals (unstable molecules with unpaired electrons)

• Carry out other oxidation-reduction reactions

Microfilament- and Microtubule- Dependent Motility

Cytoskeleton I• Microtubules

– Large diameter, hollow tubes made of tubulins

– Extend outward from the centrosome

– Anchor and transport organelles

– Very dynamic

Cytoskeleton II• Intermediate filaments

– Medium sized filament– Act as “guy wires”

Cytoskeleton III• Microfilaments

– The smallest filament– Composed of actin– Involved in cell motility and cell

shape– Responsible for muscle

contraction when actin interacts with myosin

Centrosome & Centromere• Centrosome

– Microtubule organizing center

– Contains centrioles

• Centrioles– Involved in mitosis– Give rise to cilia and flagella

DNA Replication I

Replicationbubble

Replicationfork

Unwinding of DNA by helicase

DNA Replication II

Transcription I

Transcription II

Translation I

End Chapter 3

Note: End of additional review slides.