CELLSChapter 3

Cell Theory

• Cell: structural and functional unit of life • Organismal functions depend on individual

and collective cell functions• Biochemical activities of cells dictated by their

shapes or forms, and specific subcellular structures

• Continuity of life has cellular basis

Cell Diversity

• Over 200 different types of human cells

• Types differ in size, shape, subcellular components, and functions

Plasma Membrane

• Bimolecular layer of lipids and proteins in a constantly changing fluid mosaic

• Plays a dynamic role in cellular activity• Separates intracellular fluid (ICF) from

extracellular fluid (ECF)– Interstitial fluid (IF) = ECF that surrounds cells

Membrane Lipids

• 75% phospholipids (lipid bilayer)– Phosphate heads: polar and hydrophilic– Fatty acid tails: nonpolar and hydrophobic

• 5% glycolipids– Lipids with polar sugar groups on outer membrane surface

• 20% cholesterol– Increases membrane stability and fluidity

• Lipid Rafts– ~ 20% of the outer membrane surface– Contain phospholipids, sphingolipids, and cholesterol– May function as stable platforms for cell-signaling molecules

Membrane Proteins• Integral proteins

– Firmly inserted into the membrane (most are transmembrane)

– Functions: Transport proteins (channels and carriers), enzymes, or receptors

• Peripheral Proteins– Loosely attached to integral proteins – Include filaments on intracellular surface and

glycoproteins on extracellular surface– Functions: Enzymes, motor proteins, cell-to-cell links,

provide support on intracellular surface, and form part of glycocalyx

Figure 3.3

Integralproteins

Extracellular fluid(watery environment)

Cytoplasm(watery environment)

Polar head ofphospholipid molecule

Glycolipid

Cholesterol

Peripheralproteins

Bimolecularlipid layercontainingproteins

Inward-facinglayer ofphospholipids

Outward-facinglayer ofphospholipids

Carbohydrate of glycocalyx

Glycoprotein

Filament of cytoskeleton

Nonpolar tail of phospholipid molecule

= lipid= protein

Cell Junctions• Some cells "free”• Some bound into communities– Three ways cells are bound:• Tight junctions • Desmosomes • Gap junctions

Tight Junctions• Adjacent integral proteins fuse form

impermeable junction encircling cell– Prevent fluids and most molecules from moving

between cells

Desmosomes• Anchor cells together at

plaques (thickenings on plasma membrane)– Linker proteins between cells

connect plaques– Keratin filaments (part of the

cytoskeleton) extend through cytosol to opposite plaque giving stability to cell

– Reduces possibility of tearing

Gap Junctions• Transmembrane

proteins form pores (connexons) that allow small molecules to pass from cell to cell– For spread of ions,

simple sugars, and other small molecules between cardiac or smooth muscle cells

Cell Cycle• Defines changes from formation of cell until it

reproduces• Includes:– Interphase– Cell division (mitotic phase)

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Interphase

• Period from cell formation to cell division• Nuclear material called chromatin• Three subphases:– G1 (gap 1)—vigorous growth and metabolism• Cells that permanently cease dividing said to be in G0

phase

– S (synthetic)—DNA replication occurs– G2 (gap 2)—preparation for division

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InterphaseCentrosomes (eachhas 2 centrioles)

Plasmamembrane

Nucleolus

Nuclearenvelope

Chromatin

DNA Replication

Cell Division

• Meiosis - cell division producing gametes• Mitotic cell division - produces clones– Essential for body growth and tissue repair– Occurs continuously in some cells

• Skin; intestinal lining– None in most mature cells of nervous tissue,

skeletal muscle, and cardiac muscle• Repairs with fibrous tissue

Events Of Cell Division

• Mitosis—division of nucleus– Four stages • Prophase• Metaphase• Anaphase• Telophase

– Cytokinesis—division of cytoplasm-by cleavage furrow

Prophase

Metaphase

Anaphase

Telophase and Cytokinesis

Telophase Cytokinesis

Nuclearenvelopeforming Nucleolus forming

Contractilering atcleavagefurrow

Control of Cell Division• "Go" signals:– Critical volume of cell when area of membrane

inadequate for exchange– Chemicals (e.g., growth factors, hormones)– Availability of space–contact inhibition

• To replicate DNA and enter mitosis requires– Cyclins–regulatory proteins

• Accumulate during interphase

– Cdks (Cyclin-dependent kinases)–bind to cyclins activated• Enzyme cascades prepare cell for division

– Cyclins destroyed after mitotic cell division

Control of Cell Division• Checkpoints– G1 checkpoint (restriction

point) most important• If doesn't pass G0–no

further division

– Late in G2 MPF (M-phase promoting factor) required to enter M phase

• "Other Controls" signals– Repressor genes inhibit cell

division• E.g., P53 gene

Protein Synthesis Overview

Two Components• Transcription• Translation

RNA is heavily involved

Roles of the Three Main Types of RNA

• Messenger RNA (mRNA)– Carries instructions for building a polypeptide, from

gene in DNA to ribosomes in cytoplasm• Ribosomal RNA (rRNA)– A structural component of ribosomes that, along with

tRNA, helps translate message from mRNA• Transfer RNAs (tRNAs)– Bind to amino acids and pair with bases of codons of

mRNA at ribosome to begin process of protein synthesis

Transcription

• Transfers DNA gene base sequence to a complementary base sequence of an mRNA

• Transcription factor– Loosens histones from DNA in area to be

transcribed– Binds to promoter, a DNA sequence specifying

start site of gene to be transcribed– Mediates the binding of RNA polymerase to

promoter

Transcription

• RNA polymerase– Enzyme that oversees synthesis of mRNA– Unwinds DNA template– Adds complementary RNA nucleotides on DNA

template and joins them together– Stops when it reaches termination signal– mRNA pulls off the DNA template, is further

processed by enzymes, and enters cytosol

Figure 3.35

RNA polymerase

RNA polymerase

RNApolymerase

DNA

Coding strand

Template strandPromoterregion

Terminationsignal

mRNA

mRNA

Template strand

mRNA transcript

Completed mRNA transcript

Rewindingof DNA

Coding strand of DNA

DNA-RNA hybrid region

The DNA-RNA hybrid: At any given moment, 16–18 base pairs ofDNA are unwound and the most recently made RNA is still bound toDNA. This small region is called the DNA-RNA hybrid.

Templatestrand

Unwindingof DNA

RNA nucleotides

Direction oftranscription

Initiation: With the help of transcription factors, RNApolymerase binds to the promoter, pries apart the two DNA strands,and initiates mRNA synthesis at the start point on the template strand.

Termination: mRNA synthesis ends when the termination signalis reached. RNA polymerase and the completed mRNA transcript arereleased.

Elongation: As the RNA polymerase moves along the templatestrand, elongating the mRNA transcript one base at a time, it unwindsthe DNA double helix before it and rewinds the double helix behind it.

1

2

3

Transcription

Translation

• Converts base sequence of nucleic acids into the amino acid sequence of proteins

• Involves mRNAs, tRNAs, and rRNAs• Each three-base sequence on DNA is

represented by a codon – Codon—complementary three-base sequence on

mRNA– Each codon corresponds to a specific amino acid

What do you notice about this?

How many stop codons are there?

Start codons?

Translation

• mRNA attaches to a small ribosomal subunit that moves along the mRNA to the start codon

• Large ribosomal unit attaches, forming a functional ribosome

• Anticodon of a tRNA binds to its complementary codon and adds its amino acid to the forming protein chain

• New amino acids are added by other tRNAs as ribosome moves along rRNA, until stop codon is reached

Translation

Role of Rough ER in Protein Synthesis

• mRNA–ribosome complex is directed to rough ER by a signal-recognition particle (SRP)

• Forming protein enters the ER• Sugar groups may be added to the protein,

and its shape may be altered• Protein is enclosed in a vesicle for transport to

Golgi apparatus

Figure 3.39

Ribosome

ER signalsequence

The mRNA-ribosome complex isdirected to the rough ER by the SRP.There the SRP binds to a receptor site.

Once attached to the ER, the SRP is releasedand the growing polypeptide snakes through theER membrane pore into the cisterna.

The signal sequence is clipped off by anenzyme. As protein synthesis continues, sugargroups may be added to the protein.

In this example, the completedprotein is released from the ribosomeand folds into its 3-D conformation,a process aided by molecular chaperones.

The protein is enclosed within aprotein (coatomer)-coated transportvesicle. The transport vesicles maketheir way to the Golgi apparatus,where further processing of theproteins occurs (see Figure 3.19).

Signalrecognitionparticle(SRP)

Receptor site

mRNA

Growingpolypeptide

Signalsequenceremoved

Sugargroup

Releasedprotein

Transport vesiclepinching off

Coatomer-coatedtransport vesicle

Rough ER cisterna

Cytoplasm

1 2

3

4

5

Membrane Transport

• Plasma membranes are selectively permeable• Passive Processes– No cellular energy (ATP) required– Substance moves down its concentration gradient

• Active Processes– Energy (ATP) required– Occurs only in living cell membranes

Passive Processes

• Simple diffusion– Nonpolar lipid-soluble (hydrophobic) substances

diffuse directly through the phospholipid bilayer• Facilitated diffusion– Carrier or channel mediated

• Osmosis

Passive Processes: Facilitated Diffusion

• Some lipophobic molecules (e.g., glucose, amino acids, and ions) use carrier proteins or channel proteins, both of which:– Exhibit specificity (selectivity)– Are saturable; rate is determined by number of

carriers or channels– Can be regulated in terms of activity and quantity

Facilitated Diffusion Using Carrier Proteins

• Transmembrane integral proteins transport specific polar molecules (e.g., sugars and amino acids)

• Binding of substrate causes shape change in carrier

Facilitated Diffusion Using Channel Proteins

• Aqueous channels formed by transmembrane proteins selectively transport ions or water

• Two types:– Leakage channels

• Always open

– Gated channels• Controlled by chemical or electrical signals

Passive Processes: Osmosis

• Movement of solvent (water) across a selectively permeable membrane

• Water diffuses through plasma membranes:– Through the lipid bilayer– Through water channels

called aquaporins (AQPs)

Passive Processes: Osmosis

• Water concentration is determined by solute concentration

• Osmolarity: total concentration of solute particles

• When solutions of different osmolarity are separated by a membrane, osmosis occurs until equilibrium is reached

• In Cells: When osmosis occurs, water enters or leaves a cell– Change in cell volume disrupts cell function

Tonicity

• Tonicity: The ability of a solution to cause a cell to shrink or swell

• Isotonic: A solution with the same solute concentration as that of the cytosol

• Hypertonic: A solution having greater solute concentration than that of the cytosol

• Hypotonic: A solution having lesser solute concentration than that of the cytosol

Membrane Transport: Active Processes

• Two types of active processes:– Active transport– Vesicular transport

• Both use ATP to move solutes across a living plasma membrane

Active Transport

• Requires carrier proteins (solute pumps)• Moves solutes against a concentration

gradient• Types of active transport:– Primary active transport– Secondary active transport

Primary Active Transport

• Hydrolysis of ATP (energy!) causes shape change in transport protein

• bound solutes (ions) are “pumped” across the membrane

• Sodium-potassium pump (Na+-K+ ATPase)– Located in all plasma membranes– Involved in primary (and secondary) active transport

of nutrients and ions– Maintains electrochemical gradients essential for

functions of muscle and nerve tissues

Secondary Active Transport

• Depends on an ion gradient created by primary active transport

• Energy stored in ionic gradients is used indirectly to drive transport of other solutes

• Cotransport—always transports more than one substance at a time– Symport system: Two substances transported in same

direction– Antiport system: Two substances transported in opposite

directions

Figure 3.11 step 1

The ATP-driven Na+-K+ pump stores energy by creating a steep concentration gradient for Na+ entry into the cell.

Na+-K+

pump

Cytoplasm

Extracellular fluid

1

Figure 3.11 step 2

The ATP-driven Na+-K+ pump stores energy by creating a steep concentration gradient for Na+ entry into the cell.

As Na+ diffuses back across the membrane through a membrane cotransporter protein, it drives glucose against its concentration gradientinto the cell. (ECF = extracellular fluid)

Na+-glucosesymporttransporterloadingglucose fromECF

Na+-glucosesymport transporterreleasing glucoseinto the cytoplasm

Glucose

Na+-K+

pump

Cytoplasm

Extracellular fluid

1 2

Vesicular Transport• Transport of large particles, macromolecules,

and fluids across plasma membranes• Requires cellular energy (e.g., ATP)• Functions:– Exocytosis—transport out of cell – Endocytosis—transport into cell– Transcytosis—transport into, across, and then out

of cell– Substance (vesicular) trafficking—transport from

one area or organelle in cell to another

Endocytosis and Transcytosis

• Involve formation of protein-coated (typically clathrin) vesicles

• Often receptor mediated, therefore very selective

http://www.biologycorner.com/resources/endocytosis.gif

Figure 3.12

Coated pit ingestssubstance.

Protein-coatedvesicledetaches.

Coat proteins detachand are recycled toplasma membrane.

Uncoated vesicle fuseswith a sorting vesiclecalled an endosome.

Transportvesicle containing

membrane componentsmoves to the plasma

membrane for recycling.

Fused vesicle may (a) fusewith lysosome for digestionof its contents, or (b) deliverits contents to the plasmamembrane on theopposite side of the cell(transcytosis).

Protein coat(typicallyclathrin)

Extracellular fluid Plasmamembrane

Endosome

Lysosome

Transportvesicle

(b)(a)

Uncoatedendocytic vesicle

Cytoplasm

1

2

3

4

5

6

Endocytosis

• Phagocytosis—pseudopods engulf solids and bring them into cell’s interior– Macrophages and some white blood cells

Endocytosis

• Fluid-phase endocytosis (pinocytosis)—plasma membrane infolds, bringing extracellular fluid and solutes into interior of the cell – Nutrient absorption in the small intestine

Endocytosis

• Receptor-mediated endocytosis— highly selective– Uptake of enzymes low-density lipoproteins, iron,

and insulin

Figure 3.13c

Vesicle

Receptor recycledto plasma membrane

(c) Receptor-mediatedendocytosisExtracellular substances bind to specific receptor proteins in regions of coated pits, enabling the cell to ingest and concentrate specific substances (ligands) in protein-coated vesicles. Ligands may simply be released inside the cell, or combined with a lysosome to digest contents. Receptors are recycled to the plasma membrane in vesicles.

Exocytosis

• Examples: – Hormone secretion – Neurotransmitter release – Mucus secretion – Ejection of wastes

Figure 3.14a

1 The membrane-bound vesicle migrates to the plasma membrane.

2 There, proteinsat the vesicle surface (v-SNAREs) bind with t-SNAREs (plasma membrane proteins).

The process of exocytosisExtracellular

fluid

Plasma membraneSNARE (t-SNARE)

Secretoryvesicle

VesicleSNARE(v-SNARE)

Molecule tobe secretedCytoplasm

Fusedv- and

t-SNAREs

3 The vesicleand plasma membrane fuse and a pore opens up.

4 Vesiclecontents are released to the cell exterior.

Fusion pore formed

Membrane Potential

• Separation of oppositely charged particles (ions) across a membrane creates a membrane potential (potential energy measured as voltage)

• Resting membrane potential (RMP): Voltage measured in resting state in all cells – Ranges from –50 to –100 mV in different cells– Results from diffusion and active transport of ions

(mainly K+)

Figure 3.15

1

2

3

K+ diffuse down their steep concentration gradient (out of the cell) via leakage channels. Loss of K+ results in a negative charge on the inner plasma membrane face.

K+ also move into the cell because they are attracted to the negative charge established on the inner plasma membrane face.

A negative membrane potential(–90 mV) is established when the movement of K+ out of the cell equals K+ movement into the cell. At this point, the concentration gradient promoting K+ exit exactly opposes the electrical gradient for K+ entry.

Potassiumleakagechannels

Protein anion (unable tofollow K+ through themembrane)Cytoplasm

Extracellular fluid