1

Human Cell Biology

Cell Structure and Function

Learn and Understand• Plasma membrane is like a picket fence

• Each body cell lives within a fluid environment, constantly interacting with it following the laws of chemistry and physics

• Protein conformation and protein ability to temporarily and reversibly change shape is key to life

• Cell organelles carryout specialized functions

• The presence and number of each organelle in a cell dictates what a cell can do

General Information About the CellSince 1830s, Basic/Smallest Unit Of Life• Surface to volume ratio - Cell size is optimized• What a cell can do is based on form and what it includes• About 250 different cell types in adult human

1

2

3

2

Figure 3.1 Cell diversity.

General Information About the Cell

• Requires energy – varies based on need• Most contain complete set of genetic

information

• Contain building blocks and structures to carry out activities

• Not created - come from the reproduction of other cells – humans have trillions

Basic Organization of Eukaryotic Cells -Generalized Cell

• All cells have some common structures and functions

• Human cells have three basic parts:

– Plasma membrane—flexible outer selectively-permeable boundary

– Cytoplasm—intracellular fluid containing organelles

– Nucleus—control center

4

5

6

3

Typical Eukaryotic Animal CellChromatin

Nucleolus

Smooth endoplasmicreticulum

Cytosol

Mitochon-drion

Lysosome

Centrioles

Centro-somematrix

Cytoskeletalelements

• Microtubule• Intermediatefilaments

Nuclear envelope

Nucleus

Plasmamembrane

Roughendoplasmicreticulum

Ribosomes

Golgi apparatus

Secretion being releasedfrom cell by exocytosis

Peroxisome

The Cell’s Environments

• Extracellular fluid (ECF) = interstitial fluid + blood plasma

• Intracellular fluid (ICF) = fluid inside cells

Fluids are solutions of numerous dissolved substances (solutes) and/or colloids (suspensions, not quite soluble but dispersed like a solution)

% of Body Weight

Extracellular

Fluids

Interstitial fluid 15

Blood plasma 5

Intracellular fluid 40

Plasma Membrane

• The outermost membrane

– there are many internal membranes

• Separates intracellular fluid from extracellular fluid – a 7-10 nm boundary

• Lipid bilayer and proteins in constantly changing fluid mosaic (model)

• Plays dynamic role in cellular activity

• Selectively or differentially permeable

7

8

9

4

Figure 3.3 The plasma membrane.

Extracellular fluid(watery environmentoutside cell)

Polar head of phospholipid molecule

Cholesterol GlycolipidGlyco-protein

Nonpolar tail of phospholipid molecule

Glycocalyx(carbohydrates)

Lipid bilayercontaining proteins

Outward-facinglayer ofphospholipids

Inward-facinglayer of phospholipids

Cytoplasm (watery environmentinside cell)

Integral proteins

Filament of cytoskeleton

Peripheral proteins

Note:

Glycocalyx

is unique to

an

individual’s

cells and

identifies

cells to

each other.

Also

identifies

non-self.

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– Increasing cholesterol increases membrane

stability, reduces fluidity

Membrane Lipids

Fluid nature provides/allows

• Distribution of molecules within the membrane to change

• Growth and repair– Phospholipids reassembled if membrane is damaged or

altered – self orienting

• PM incorporates other membranes or segments can ‘break away’

• One reason for selective permeability

10

11

12

5

PhospholipidsPolar (hydrophilic) at

one end; nonpolar (hydrophobic) at the other.

Do you remember polarity?

What about electronegativity?

Membrane Proteins

• Improve communication with environment

• ½ mass of plasma membrane

• Most carry out specialized membrane functions

• Some chemically anchored and move freely

• Some tethered to intracellular structures

• Two types

13

14

15

6

• Integral proteins

– Firmly inserted into membrane

• most are transmembranal

– hydrophobic and hydrophilic regions place them in membrane

• Can interact with lipid tails and water

– Function as transport proteins (channels and carriers), enzymes, or receptors

Membrane Proteins

• Peripheral proteins

– Loosely attached to integral proteins

– Include filaments on intracellular surface for membrane support

– Function as enzymes; motor proteins for shape change during cell division and muscle contraction; cell-to-cell connections

Membrane Proteins

Summary of Membrane Protein Function• Transport• Receptors • Attachment to extracellular proteins or

other cells• Enzymes• Cell-cell recognition

Critical Learning Objective:• Function dependent on 3-D shape

(conformation) and chemical characteristics.

• Conformation dependent on amino acids present, bonding, and environment

• Conformational Shift - a result of the R groups of the amino acids that make up the proteins

16

17

18

7

Protein Basicsamine Carboxyl (acid)

hydrophilic

Neutral/hydrophobic

Acidic side group -hydrophilic

A “dipeptide”

Figure 2.22 Levels of protein structure.

• Channel: A protein that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute.

• Carrier: Some transport proteins hydrolyze ATP as an energy source to actively pump substances across the membrane.

• Not all carriers utilize ATP

Transport

ATP →ADP + P + free energy

19

20

21

8

A membrane protein exposed to the outside of the cell may have a binding site that fits the shape of a specific chemical messenger, such as a hormone.

When bound, the chemical messenger may cause a change in shape in the protein that initiates a chain of chemical reactions in the cell.

Contact signaling—touching and recognition of cells

Chemical signaling—interaction between receptors

and ligands to alter activity of cell proteins

Signal

Receptor

ReceptorsActive site or

binding site

Signal Transduction using the G protein messaging system

Ligand (1st messenger)

Receptor G protein Enzyme 2ndmessenger

Effector protein

(e.g., an enzyme)

Extracellular fluid

G protein

GDP

Intracellular fluid

Cascade of cellular responses (The amplification effect istremendous. Each enzyme

catalyzes hundreds of reactions.)

Activatedkinaseenzymes

Active 2ndmessenger

Inactive 2nd

messenger

* Ligands includehormones andneurotransmitters.

ReceptorLigand

membrane protein may be an enzyme with its active site exposed to substances in the adjacent solution

Example: final digestion of biomolecules at membrane of intestinal cells

A team of several enzymes in a membrane may catalyze sequential steps of a metabolic pathway

Enzymes

Enzymatic activity

22

23

24

9

Attachment to the internal cytoskeleton and/orextracellular matrix

Elements of the cytoskeleton (cell's internal supports) and the extracellular matrix (basement membrane) may anchor to membrane proteins, which helps maintain cell shape and fix the location of certain membrane proteins.

Others play a role in cell movement or bind adjacent cells together.

CAMs

Intercellular Joining - Cell Junctions

• Some cells free roaming– e.g., sperm cells, several cells of

immune system

• Many cells bound into communities– Membrane proteins of adjacent

cells may be hooked together in various kinds of intercellular junctions.

– Three ways cells are bound

cell adhesion molecules or CAMs

Plasma membranesof adjacent cells

Microvilli

Intercellularspace

Basement membrane

Interlockingjunctionalproteins

Intercellularspace

Tight junctions: Impermeable junctionsprevent molecules from passing throughthe intercellular space.

25

26

27

10

Intercellularspace

Linkerproteins(cadherins)Intermediate

filament(keratin)

Plaque

Desmosomes: Anchoring junctions bind adjacent cells together like a molecular “Velcro” and help form an internal tension-reducing network of fibers.

Sheet-like tissues

Microvilli

Intercellularspace

Basement membrane

Plasma membranesof adjacent cells

Plasma membranesof adjacent cells

Microvilli

Intercellularspace

Basement membrane

Intercellularspace

Channelbetween cells(formed byconnexons)

Gap junctions: Communicating junctions allow ions and small molecules to pass for intercellular communication.

Cardiac muscle, smooth muscle, some neurons

• Some glycoproteins serve as identification tags that are specifically recognized by other cells.

Glycoprotein

Cell-Cell Recognition

28

29

30

11

Passage of Materials Across the Membrane

• Plasma membranes selectively permeable– Some molecules pass through easily; some do not

• Passage of a molecule is the result of chemical properties (polarity/charge), size, availability of specific channels or carriers, electrochemical gradient– some substances pass easily through lipid bilayer– some pass through channel and carrier proteins– some must be ‘pumped’ across using carrier proteins

and energy– some must be engulfed

Types of Membrane Transport• Passive processes

– No cellular energy (ATP) required– Substance moves down its concentration or electrical gradient

• High to low concentration; positive charge toward negative charge; until equilibrium

– Diffusion• Simple diffusion

– Osmosis, the diffusion of solvent (water) based on solute concentration– If you need to, review osmosis and tonicity – Osmolarity = sum of the molarities of the dissolved particles of a solution mOsm/l

• Facilitated diffusion – “assisted”– Carrier- and channel-mediated – involves some of the those proteins just presented

• Influenced by temperature

– Filtration• Based on size of openings, size of molecules, pressure• More commonly occurs in-between cells rather than across membranes

• Active processes– Energy (ATP) required which can only be provided by a living cell

Figure 3.7a Diffusion through the plasma membrane.

Extracellular fluid

Lipid-solublesolutes

Cytoplasm

Simple diffusion of fat-soluble molecules directly through the phospholipid bilayer

Passive Processes:

31

32

33

12

Figure 3.7c Diffusion through the plasma membrane.

Small lipid-insoluble solutes

Channel-mediated facilitated diffusionthrough a channel protein; mostly ions selected on basis of size and charge

Passive Processes:

A “leakage channel” –

always open

Compare to a gated

channel that requires a

stimulus to open

Figure 3.7d Diffusion through the plasma membrane.

Osmosis, diffusion of a solvent such as water through a specific channel protein (aquaporin) or through the lipid bilayer

Watermolecules

Lipidbilayer

Aquaporin

Passive Processes:

Figure 3.7b Diffusion through the plasma membrane.

Lipid-insoluble solutes (such as sugars or amino acids)

Carrier-mediated facilitatedDiffusion via protein carrier specificfor one chemical; binding of substratecauses transport protein to change shape

Passive Processes:

Conformational

shift of the

protein moves

the molecule

34

35

36

13

Carrier Protein Dynamics

Lessons:

• Carriers/facilitators are specific, carry only compatible molecules

• Competitors/inhibitors alter ability to carry compatible molecules

• Carrying/facilitating takes time, albeit brief

• The number of carriers/facilitators in cell membrane is finite – the cell controls the number

and type – up/down regulation possible

Membrane Transport: Active Processes

• Two types of active processes– Active transport

– Vesicular transport

• Both require ATP to move solutes across a living plasma membrane because: – Solute too large (example: proteins) for channels

and/or

– Solute not lipid soluble and/or

– No concentration gradient

Active Transport: Two Types

• Requires carrier proteins (solute ‘pumps’)

– Bind specifically and reversibly with substance

• Moves solutes against concentration gradient

• Primary active transport

– Required energy directly from ATP hydrolysis

• Secondary active transport

– Required energy indirectly from ionic gradients created by primary active transport

37

38

39

14

Primary Active Transport

• Energy from hydrolysis of ATP causes shape change in transport protein that "pumps" solutes (ions) across membrane– Solute binding and phoshorylation cause conformational

changes in transport protein

• E.g., calcium, hydrogen, Na+-K+ pumps• Sodium-potassium pump

– Most well-studied– Carrier (pump) called Na+-K+ ATPase– Located in all plasma membranes– Involved in primary and secondary active transport of

nutrients and ions

Figure 3.10 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP.

Extracellular fluidNa+

Na+–K+ pump

K+

ATP-binding site

Cytoplasm

1 Three cytoplasmic Na+ bind to pump

protein.

K+ released

6 Pump protein binds ATP; releases K+ to

the inside, and Na+ sites are ready to bind

Na+ again. The cycle repeats.

2 Na+ binding promotes hydrolysis of ATP.

The energy released during this reaction

phosphorylates the pump.

K+ bound

5 K+ binding triggers release of the

phosphate. The dephosphorylated pump

resumes its original conformation.

K+

4 Two extracellular K+ bind to pump.

3 Phosphorylation causes the pump to

change shape, expelling Na+ to the outside.

Na+ bound

Na+ released

P

P

P

Pi

Figure 3.11 Secondary active transport is driven by the concentration gradient

created by primary active transport.

Extracellular fluid

Na+-glucosesymporttransporterloads glucosefrom extracellularfluid

Na+-glucosesymport transporterreleases glucoseinto the cytoplasm

Glucose

Na+-K+

pump

Cytoplasm

Active Transport Terms:

Uniport - always transports one substance at a time (not shown)

Cotransport - always transports more than one substance at a time

Symport system: Substances transported in same direction

Antiport system: Substances transported in opposite directions

40

41

42

15

Vesicular Transport

• Transport of large particles, macromolecules, and fluids across membrane in membranous sacs called vesicles

• Requires cellular energy

• Functions:– Exocytosis—transport out of cell

– Endocytosis—transport into cell• Phagocytosis, pinocytosis, receptor-mediated endocytosis

– Transcytosis—transport into, across, and then out of cell

– Vesicular trafficking—transport from one area or organelle in cell to another

Phagocytosis and Receptor-Mediated Endocytosis

Receptors

Phagosome

Vesicle

pseudopods

Pinocytosis and Exocytosis Captured in Living Cell

Vesicle

Photomicrograph of a secretoryvesicle releasingits contents by exocytosis (100,000x)

43

44

45

16

Figure 3.12 Events of endocytosis mediated by protein-coated pits.1

Protein coat(typicallyclathrin)

Transportvesicle

EndosomeUncoated endocyticvesicle

Transport vesicle containing

Uncoated vesicle fuses with a sorting vesicle called an endosome.

Fused vesicle may (a) fuse with lysosome for digestion of its contents, or (b) deliver its contents to the plasma membrane on the opposite side of the cell (transcytosis).

Extracellular fluidPlasma membrane

Cytoplasm

Lysosome

2

membrane compone-nts moves to the plasmamembrane for recycling.

3

54

6

Cell Organelles

Cytoplasm

• Cellular material outside nucleus but insideplasma membrane

• Composed of – Cytoskeleton– Cytosol: semi-fluid portion.

• Dissolved molecules (ions in water) • A colloid (suspension of semi-soluble substances,

example: proteins in water)

– Cytoplasmic Inclusions – granules, droplets, pigment molecules, crystals

– Organelles

46

47

48

17

Nucleus

• Membrane-bound

• Nucleoplasm, nucleolus and nuclear envelope

• Much of the DNA in a cell located here

Figure 3.25 The nucleus.

Cytoskeleton• Supports the cell but has to allow for

movements like changes in cell shape and movements of cilia

Microtubules: hollow, made of tubulin.

Internal scaffold, transport, cell division

Intermediate filaments: mechanical strength

Microfilaments: actin.

Structure, support for microvilli, contractility, movement

• Cytoplasmic inclusions: aggregates of chemicals such as lipid droplets, melanin

49

50

51

18

Figure 3.20 Cytoskeletal elements support the cell and help to generate movement.

• Nonmembranous– Cytoskeleton

– Centrioles

– Ribosomes

• Membranes allow crucial compartmentalization

Cytoplasmic Organelles

• Membranous

– Mitochondria

– Peroxisomes

– Lysosomes

– Endoplasmic reticulum

– Golgi apparatus

Ribosomes

• Sites of protein synthesis

• Composed of a large and a small rRNA subunit

• Types

– Free

– Attached (to endoplasmic reticulum)

52

53

54

19

Endoplasmic Reticulum

• Types– Rough

• Has attached ribosomes• Proteins produced and modified here• Common in cells that secrete protein products

– Smooth• No attached ribosomes, instead integral proteins serving

as enzymes• Manufacturing, metabolism, breakdown• More specialized function in muscle cells

– Cisternae: Interior spaces isolated from rest of cytoplasm

Figure 3.18 The endoplasmic reticulum.

Nucleus

Smooth ER

Nuclearenvelope

Rough ER

Ribosomes

Electron micrograph of smooth and roughER (25,000x)

Diagrammatic view of smooth and rough ER

Figure 3.39 Rough ER processing of proteins. Slide 1

The SRP directs themRNA-ribosome complex to therough ER. There the SRP binds toa receptor site.

Once attached to the ER, the SRP isreleased and the growing polypeptidesnakes through the ER membrane poreinto the cistern.

An enzyme clips off the signal sequence. As protein synthesiscontinues, sugar groups may beadded to the protein.

In this example, the completed proteinis released from the ribosome and foldsinto its 3-D conformation, a process aidedby molecular chaperones.

The protein is enclosed within aprotein coated transport vesicle. Thetransport vesicles make their way tothe Golgi apparatus, where furtherprocessing of the proteins occurs(see Figure 3.19).

Signalrecognitionparticle(SRP)

Receptor site

Rough ER cistern

Growingpolypeptide

Signalsequenceremoved

Sugargroup

Releasedprotein

ER signalsequence

Ribosome

mRNA

CytosolTransport vesiclepinching off

Protein-coatedtransport vesicle

1 2

3

4

5

55

56

57

20

Figure 3.16 Golgi apparatus.

Figure 3.20 The sequence of events from protein synthesis on the rough ER to the final distribution of those proteins.

ER membrane

Phagosome

Proteins incisterns

Plasmamembra-ne

Pathway C:Lysosomecontaining acidhydrolaseenzymesVesicle

becomeslysosome

Pathway B:Vesicle membraneto be incorporatedinto plasmamembrane

Extracellular fluidSecretion byexocytosis

Pathway A:Vesicle contentsdestined forexocytosis

Golgi apparatus

Secretoryvesicle

Rough ER

Vesicular

trafficking

Action of Lysosomes

58

59

60

21

Mitochondria• Major site of ATP synthesis

• Membranes– Cristae: Infoldings of inner

membrane

– Matrix: Substance located in space formed by inner membrane

• Mitochondria increase in number when cell energy requirements increase.

• Mitochondria contain DNA that codes for some of the proteins needed for mitochondria production.

Overview of Cell Metabolism

• Production of ATP necessary for life

• ATP production takes place in the cytosol (anaerobic) and mitochondria (aerobic)– Anaerobic does not require

oxygen. Results in very little ATP production but provides ATP when O2 is in short supply.

– Aerobic requires oxygen. Results in large amount of ATP.

Cilia

• Appendages projecting from cell surfaces

• Capable of movement• Moves materials over

the cell surface

61

62

63

22

Figure 3.23 Ciliary function.

Flagella

• Similar to cilia but longer

• Usually only one per cell

• Move the cell itself in wave-like fashion

• Example: sperm cell

64

65