Ch 2, CELLS: The Living Units Ch 2, CELLS: The Living Units of Organismsof Organisms

Sonya Schuh-Huerta, Ph.D.Sonya Schuh-Huerta, Ph.D.

Human embryonic stem cells, S. Huerta

The Inner Life of the Cell…

Introduction to Cells

• Several important scientists made discoveries about cells– Antonie van Leeuwenhoek – one of 1st to observe cells;

father of microscopy & microbiology

– Robert Hooke – coined the term “cell” as the basic unit of life

– Matthias Schleiden & Theodor Schwann – Rudolf Virchow

• Cells – the smallest living units in our bodies– Organelles “little organs” – carry on essential functions

of cells

Introduction to Cells

• Cells have 3 main components– Plasma membrane = the outer boundary– Cytoplasm = contains most organelles– Nucleus = controls cellular activities

Structure of a Generalized Cell

Secretion being released from cell by exocytosis

Peroxisome

Ribosomes

Roughendoplasmicreticulum

Nucleus

Nuclear envelopeChromatin

Golgi apparatus

Nucleolus

Smooth endoplasmicreticulum

Cytosol

Lysosome

Mitochondrion

Centrioles

Centrosomematrix

Microtubule

Cytoskeletalelements

Intermediate filaments

Plasmamembrane

The Plasma Membrane

• Defines the extent of the cell

• Structure of membrane– Fluid mosaic model (lipid bilayer)– Types of membrane proteins:

• Integral proteins = firmly imbedded in, or attached to lipid bilayer

• Short chains of carbohydrates attach to integral proteins - form the glycocalyx

• Peripheral proteins = attach to membrane surface

– Support plasma membrane from cytoplasmic side

The Plasma Membrane

Integral proteins

Extracellular fluid(watery environment)

Cytoplasm (watery environment)

Polar head of phospholipid molecule

GlycolipidCholesterol

Peripheralproteins

Bimolecular lipid layercontaining proteins

Inward-facing layer of phospholipids

Outward-facing layer of phospholipids

Carbohydrate of glycocalyx

GlycoproteinNonpolar tail of phospholipid molecule

Filament of cytoskeleton

The Plasma Membrane

• Functions – relate to location at the interface of cell’s exterior and interior– Acts as barrier against substances outside cell– Cell-to-cell recognition & communication (receptors)– Determines which substances enter or leave the cell

• Plasma membrane is selectively permeable!

The Plasma Membrane in Action

Membrane Transport

• Simple diffusion – tendency of molecules to move down their concentration gradient

• Osmosis – diffusion of water molecules across a membrane – down their gradient

Membrane Transport Mechanisms

• Facilitated diffusion = movement of molecules down their concentration gradient through an integral protein

• Active transport = integral proteins move molecules across the plasma membrane against their concentration gradient (often using energy in the form of ATP)

Membrane Transport Mechanisms

Extracellular fluid

Lipid-solublesolutes

Cytoplasm

Watermolecules

Solutes

Lipidbilayer

Simple diffusion Osmosis Facilitated diffusion & active transport

Endocytosis

• Endocytosis– Mechanism by which particles enter cells

• Phagocytosis = “cell eating”• Pinocytosis = “cell drinking”

Receptor-Mediated Endocytosis

• Receptor-mediated endocytosis = plasma proteins bind to certain molecules & bring them into the cell

• Invaginates and forms a coated pit – Pinches off to become a coated vesicle

• NOTE: This process is very specific to certain molecules.

• It is the method by which insulin and cholesterol enter cells!

3 Types of Endocytosis

Phagosome

Vesicle

Vesicle

Receptor recycledto plasma membrane

Phagocytosis Pinocytosis

Receptor-Mediated Endocytosis

Exocytosis

• Exocytosis = mechanism that moves substances out of the cell– Substance is enclosed in a vesicle– The vesicle migrates to the plasma membrane– Proteins from the vesicles (v-SNAREs) bind with

membrane proteins (t-SNAREs)– The lipid layers from both membranes bind & the vesicle

releases its contents to the outside

Exocytosis

The membrane-bound vesicle migrates to the plasma membrane.

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

The vesicle and plasma membrane fuse and a pore opens up.

Vesicle contentsare released to the cell exterior.

Extracellularfluid

Plasma membraneSNARE (t-SNARE)

Secretoryvesicle Vesicle SNARE

(v-SNARE)

Molecule tobe secreted

Fusedv- andt-SNAREs

Fusion pore formed

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Cytoplasm

Exocytosis in Action

The Cytoplasm

• Cytoplasm = lies internal to plasma membrane

& consists of cytosol, organelles, & inclusions

• Cytosol = jelly-like fluid in which other cellular elements are suspended– Consists of water, ions, & enzymes

Organelles – Ribosomes

• Ribosomes – constructed of proteins and ribosomal RNA; not surrounded by a membrane

– Site of protein synthesis• Assembly of proteins is called translation

– Are the “assembly line” of the manufacturing plant

Endoplasmic Reticulum

• Endoplasmic reticulum—“network within the cytoplasm”

Rough ER – ribosomes stud the external surfaces

Smooth ER – consists of tubules in a branching

network• No ribosomes are attached; therefore no protein

synthesis

The ER & Ribosomes

Nuclearenvelope

Ribosomes

Rough ER

(a) Diagrammatic view of smooth and rough ER

Smooth ER

(b) Electron micrograph of smooth and

rough ER (85,000)

Cisternae

Golgi Apparatus

• Golgi apparatus = a stack of 3–10 disk-shaped envelopes

– Sorts products of rough ER and sends them to proper destination

– Products of rough ER move through the Golgi from the convex (cis) to the concave (trans) side

– “Packaging & shipping” division of manufacturing plant

Golgi Apparatus

Cis face—“receiving” side of Golgi apparatus

Secretory vesicle

Many vesicles in the process of pinching off from the membranous Golgi apparatus

Electron micrograph of the Golgi apparatus (90,000)

Transport vesicle from the Golgi apparatus

Transportvesiclefromtrans face

Trans face –“shipping” side ofGolgi apparatus

New vesiclesforming

New vesicles forming

Cisternae

Transport vesiclefrom rough ER

Golgi apparatus

Lysosomes• Lysosomes = membrane-walled sacs containing

digestive enzymes– Digest substances– Cells of gut many lysosomes

Lysosomes

Plasmamembrane

Secretion by exocytosis

Vesicle becomeslysosome

Golgi apparatus

Rough ER ER membrane Phagosome

Proteins in cisterna

Pathway B:Vesicle membraneto be incorporatedinto plasmamembrane

Pathway A:Vesicle contentsdestined forexocytosis Extracellular fluid

Secretoryvesicle

Pathway C: Lysosomecontaining acid hydrolaseenzymes

Protein-containing vesicles pinch off rough ER and migrate to fuse with membranes of Golgi.

Proteins are modified within the Golgi compartments.

Proteins are then packaged within different vesicle types, depending on their ultimate destination.

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Sequence of Events From Protein Synthesis to Their Final Distribution

Mitochondria

• Mitochondria = generates most of the cell’s energy; most complex organelle; Arose from early animal cell engulfing a prokaryote – they then lived together happily ever after!

– More abundant in energy- requiring cells, like muscle cells & sperm

– “Power plant” of the cell

Mitochondria

Enzymes

Matrix

Cristae

Mitochondrial DNA

Ribosome

Outer mitochondrial membrane

Innermitochondrial membrane

Peroxisomes

• Peroxisomes = membrane-walled sacs of oxidase enzymes – Enzymes neutralize free radicals and break down

poisons (ie. alcohol, hydrogen peroxide)– Break down long chains of fatty acids– Are the toxic waste removal system – Are numerous in the liver and kidneys!!!

The Cytoskeleton

• Cytoskeleton = “cell skeleton” – an elaborate network of protein rods

– Contains 3 types of rods:• Microtubules = cylindrical structures made of tubulin protein

subunits; form mitotic spindle and are the tracks that motor proteins transport materials on

• Intermediate filaments = protein fibers; provide structure and rigidity to cell

• Microfilaments = filaments of the contractile protein actin; perform contractile functions of cell

(a) Microfilaments

Strands made of spherical proteinsubunits called actins

(b) Intermediate filaments

Tough, insoluble protein fibersconstructed like woven ropes

(c) Microtubules

Hollow tubes of spherical proteinsubunits called tubulins

Actin subunit

7 nm 10 nm 25 nm

Fibrous subunitsTubulin subunits

Cytoskeletal Elements

The Cytoskeleton in Action

Centrosome

• Centrosomes & centrioles:

– Centrosome = a spherical structure in the cytoplasm• Composed of centrosome matrix and centrioles

– Centrioles = paired cylindrical bodies made of tubulin• Each consists of 27 short microtubules• Act in forming cilia & flagella• Gives rise to mitotic spindle - necessary for

karyokinesis (nuclear division)

Centrosome matrix

Centrioles

Microtubules

Centrosome & Centrioles

Cytoplasmic Inclusions

• May consist of pigments, crystals of protein, and food stores (temporary structures, not present in all cell types)

– Lipid droplets – found in liver cells & fat cells– Glycosomes – store sugar in the form of glycogen

The Nucleus

• Nucleus = “little nut” or “kernel” – control center

of cell

– DNA directs the cell’s activities & production of proteins– ~5 µm in diameter

The Nucleus

• Nuclear envelope = two parallel membranes separated by fluid-filled space

• Nuclear pores penetrate the nuclear envelope– Pores allow large molecules to pass in and out of the

nucleus (like messenger RNA)

The Nucleus

• Nucleolus = “little nucleus” – in the center of the nucleus

– Contains parts of several chromosomes– Site of ribosome subunit assembly

The Nucleus

Chromatin (condensed)

Nuclear envelope Nucleus

Nuclearpores

Fractureline of outermembrane

Nuclear pore complexes. Each pore is ringed by protein particles

Nuclear lamina. The netlike lamina composed of intermediate filaments formed by lamins lines the inner surface of the nuclearenvelope.

Nucleolus

Cisternae of rough ER

Chromatin & Chromosomes

• DNA double helix is composed of a sugar phosphate backbone and four subunits:– Thymine (T), adenine (A), cytosine (C), & guanine (G)

• DNA is coiled around proteins (histones)– DNA + proteins = chromatin

Chromatin & Chromosomes

• Each cluster of DNA & histone proteins is a nucleosome Deoxyribose

sugar

PhosphateSugar-phosphatebackbone

Hydrogen bond

Adenine (A)

Thymine (T)

Cytosine (C)

Guanine (G)

Nucleotides

Chromatin & Chromosomes• Extended chromatin

– Is the active region of DNA where DNA’s genetic code is duplicated (in replication) or copied into messenger RNA (mRNA) in the process of transcription

• Condensed chromatin– Tightly coiled nucleosomes– Inactive form of chromatin – no transcription

occurring

• Chromosomes = highest level of organization of chromatin– Contains a long molecule of DNA– Typical human cell has 46 chromosomes!

Chromatin & Chromosome Structure

MetaphaseChromosome = 2 sister chromatids(at midpoint of cell division)

Nucleosome (10-nm diameter; 8 histone proteins wrappedby 2 winds of the DNA double helix)

Linker DNA

Histones

DNA doublehelix (2-nm diameter)

Chromatin (“beads on a string”) structure with nucleosomes

Tight helical fiber(30-nm diameter)

Chromatid(700-nm diameter)

Looped domain structure (300-nm diameter)

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The Cell Life Cycle

• The cell life cycle = the series of changes a cell goes through, including dividing & producing daughter cells

– Interphase:

• G1 phase = Growth 1 or Gap 1 phase– The first part of interphase– Cell metabolically active grows & makes proteins– Variable in length from hours to YEARS! (egg cell)– Centrioles begin to replicate near the end of G1

The Cell Life Cycle

• S (synthesis) phase = DNA replicates itself– Ensures that daughter cells receive identical copies of

the genetic material (chromatin extended)

• G2 phase = Growth 2 or Gap 2– Centrioles finish copying themselves (now 2 pairs!)– Enzymes needed for cell division are synthesized

• During S & G2 phases of interphase cell carries on normal activities

The Cell Life Cycle

• Cell division = mitosis

– M (mitotic) phase = cells divide during this stage

• Comes after interphase (G1, S, & G2)

Cell Division

• Cell division involves:

– Mitosis = division of the nucleus• Chromosomes are distributed to the 2 daughter

nuclei

– Cytokinesis = division of the cytoplasm• Occurs after the nucleus divides

G1

Growth

SGrowth and DNA

synthesis G2

Growth and finalpreparations for

divisionM

G2 checkpoint

G1 checkpoint(restriction point)

Mitotic phase (M)Cytokinesis

Telo

ph

ase

An

aph

aseM

etaphaseProphase

Interphase

Mitosis

The Cell Life Cycle

Stages of Mitosis

• Prophase = 1st & longest stage of mitosis

– Early prophase chromatin threads condense into chromosomes

• Chromosomes = 2 threads called chromatids (sister chromatids)

• Chromatids held together by the centromere• Centriole pairs separate from one another• Mitotic spindle forms

– Late prophase centrioles continue moving away from each other

• Nuclear membrane breaks down• Chromosomes bound by mitotic spindle

Early & Late Prophase

Centrosomes (eachhas 2 centrioles)

Early mitoticspindle

Spindle pole

Kinetochore Kinetochoremicrotubule

Polar microtubule

Nucleolus Centromere

Plasmamembrane Fragments

of nuclearenvelopeAster

Nuclearenvelope

Chromosomeconsisting of twosister chromatids

Chromatin

Interphase Early Prophase Late Prophase

Stages of Mitosis

• Metaphase = 2nd stage of mitosis– Chromosomes cluster at middle of the cell

• Centromeres are aligned along the equator

• Anaphase = 3rd & shortest stage of mitosis– Centromeres of chromosomes split apart

Stages of Mitosis

• Telophase = 4th stage of mitosis – Begins as chromosomal movement stops– Chromosomes at opposite poles of the cell uncoil– Resume threadlike extended-chromatin form– A new nuclear membrane forms

• Cytokinesis = completes the division of the cell into 2 daughter cells

Metaphase, Anaphase,Telophase & Cytokinesis

Contractilering atcleavagefurrow

Nuclearenvelopeforming

Nucleolus forming

Spindle

Metaphaseplate

Daughterchromosomes

Metaphase Anaphase Telophase & Cytokinesis

Mitosis in Action

Cellular Diversity

• Specialized functions of cells relates to:– Shape of cell morphology– Arrangement, types, & numbers of organelles

• Cellular Differentiation– Cells in different regions of developing embryo are

exposed to different chemical signals– Cells differentiate into different cell types &

become specialized

Cellular Diversity

• Cells that connect body parts or line & cover organs:

– Fibroblast = makes and secretes protein component of fibers– Erythrocyte = concave shape provides surface area for uptake

of the respiratory gases– Epithelial cell = hexagonal shape allows maximum number of

epithelial cells to pack together

Cellular Diversity

• Cells that MOVE organs & body parts:

– Skeletal & smooth muscle cells• Elongated & made of actin & myosin• Contract forcefully!

Skeletalmusclecell

Smoothmuscle cells

Cellular Diversity

• Cells that store nutrients:– Fat cell = stores fat; shape is

produced by large fat droplet in

its cytoplasm

• Cells that fight disease:– Macrophage = moves through tissue to reach

infection sites & engulfs foreign particles

Macrophage

Fat cell

Cellular Diversity

• Cells that gather & transmit information:– Neuron = has long processes for receiving &

transmitting messages

neuron

Cellular Diversity• Cells of reproduction:

*Sperm (male) = specialized cell with a

long tail (flagellum) for swimming to and

fertilizing the egg

*Oocyte (female) = largest cell of the body, contains

extra stores of RNA and protein, specialized outer

shell

Developmental Aspects of Cells

• Aging = complex process that happens over time; caused by a variety of factors:

– Free radical theory• Damage from byproducts of cellular metabolism• Radicals build up & damage essential molecules of cells

– Mitochondrial theory• A decrease in production of energy by mitochondria weakens

& ages our cells

– Genetic theory = proposes that aging is programmed by genes

• Telomeres = “end caps” on chromosomes

• Telomerase = prevents telomeres from degrading

Questions…?

What’s Next?Lab: The Microscope & Cells Wed Lecture: Embryology & TissuesWed Lab: Cells & Tissues