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Cells and the Stuff They ’ re Made of …. Cells are the “ indivisible ” units of life. There is nothing smaller that is alive, nothing bigger is more alive. - J. Theriot. Metabolism: Cells consume energy from environment and use it to create ordered structures.

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cells are the indivisible units of life
Cells are the “indivisible” units of life.

There is nothing smaller that is alive, nothing bigger is more alive. - J. Theriot

  • Metabolism: Cells consume energy from environment and use it to create ordered structures.
  • Replication: Cells harness energy from environment to create offspring.

Standard definition of life merges metabolism and replication:

Common ancestor several billion years ago, gave rise to three major cell types:

Archaea, Bacteria, Eukaryota

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prokaryotes and eukaryotes
Prokaryotes and Eukaryotes

Prokaryotes: absence of nuclear membrane (and other organelles)

Bacterium

Eukaryotes: presence of nuclear membrane

Fibroblast

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e coli as the standard ruler
E. coli as theStandard Ruler

E. Coli is the “hydrogen atom” of cell biology.

“Not everyone is mindful of it, but cell biologists have two cells of interest; the one they are studying and Escherichia coli.” – Schaechter et al.

  • Easy to isolate
  • Able to grow in the presence of oxygen
  • Replicates rapidly
  • Easy to generate mutants

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hierarchy of spatial scales
Hierarchy of Spatial Scales

Fly

Sperm Cell

Compound Eyes

Bacterium

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Bacteriophage

ATPase

Water Molecule

DNA

some different cell types
Some Different Cell Types

Referenced to E. coli as the standard ruler

A: Giardia lamblia

B: Plant cell

C: S. cerevisiae

D: Red blood cell

E: Fibroblast cell

F: Nerve cell

G: Rod cell

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cellular interior organelles
Cellular Interior: Organelles

Red: Nucleus

Yellow: Golgi

Green: Microtubules

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energy production mitochondria
Energy Production: Mitochondria

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how do we know about cellular and subcellular structures
How do we know about cellular and subcellular structures?

Common techniques:

(A) fluorescence microscopy

(B) atomic force microscopy

(C) electron microscopy

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cellular interiors molecular parts
Cellular Interiors: Molecular Parts

Proteins, Nucleic Acids, Lipids, Carbohydrates:

  • Each class can be assembled by the cell from a small number of simpler subunits or precursor molecules
  • A cell needs only a restricted repertoire of biochemical reactions to synthesize the subunits from food in the environment
  • Combinatorial assembly of subunits gives rise to huge structural diversity making up the stuff of cells

A: DNA (nucleic acid)

B: Hemoglobin (protein)

C: Phosphatidylcholine (lipid)

D: Branched carbohydrate

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examples of molecular types
Examples of Molecular Types

Glucose

Galactose

DNA

Phosphatidylcholine

Hemoglobin

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two great polymer languages
Two “Great Polymer Languages”

Alphabet:

Nucleotides (4)

Amino Acids (20)

Words:

Codon (3 nucleotides)

Elements of secondary structure

Sentences:

Genes (~4500 in E. coli)

Fully folded proteins

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macromolecular assemblies by shape
Macromolecular Assemblies (by shape)

Helical protein assemblies are ubiquitous.

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macromolecular assemblies by function
Macromolecular Assemblies (by function)

Proteins, nucleic acids, lipids,

sugars acting as a team

(“-somes”): ~10 nm scale

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macromolecular superstructures
Macromolecular Superstructures
  • Ribosomes on ER
  • Myosin filaments in myofibrils in muscle cells
  • Microvilli at epithelial surface

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molecular representation
Molecular Representation
  • Ball-and-stick
  • Space-filling
  • Ribbon

Atomic level structure revealed through:

X-ray crystallography

Nuclear magnetic resonance (NMR)

Cryo-electron microscopy

Leading to:

diagrams.

Eg. Triose phosphate isomerase:

Enzyme involved in glycolysis pathway

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molecular composition of bacterial cell
Molecular Composition of (Bacterial) Cell

Molecular Class % of total cell weight

Small Molecules (74%)

ions, inorganic molecules 1.2

sugars 1

fatty acids 1

individual amino acids 0.4

individual nucleotides 0.4

water 70

Medium and Big Molecules (26%)

protein 15

DNA 6

RNA 1

lipids 2

polysaccharides 2

(From Alberts, et al., MBoC)

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fantastic voyage
Fantastic Voyage …

Movie available at:

See also D. Liu, “Seeing Cells on the Web”:

http://www.lifescied.org/cgi/content/full/6/1/21

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slide22
Science is built up of facts, as a house is with stones. But a collection of facts is no more a science than a heap of stones is a house. - Henri Poincare

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molecular census
Molecular Census

Why do we care about numbers of different molecules inside the cell?

  • Quantitative understanding of cellular phenomena requires quantitative knowledge of the numbers of key players (molecules) involved and the spatial dimensions over which they act.
  • Molecular counts will determine rates of macromolecular synthesis during the cell cycle (genome replication, protein synthesis rates).
  • Small or large molecular copy numbers determine the qualitative nature of chemical reactions (stochastic vs deterministic).

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sizing up e coli
Sizing up E. coli

Estimate:

Nprotein, Nribosome, Nlipid, NH20, Nion !!

… back to the chalkboard.

Conclusion:

The cell is a very crowded place!

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recap hierarchy of spatial scales
Recap …Hierarchy of Spatial Scales

Hierarchy of spatial scales:

Atom

DNA

Organelles

Virus

Bacterial Cell

Eukaryotic Cell

Multicellular Aggregates

Tissue

Organism

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spatial organization at the cellular level
Spatial Organization at the Cellular Level

Organelles (nucleus, ER, Golgi apparatus, lysosome …)

Macromolecular superstructures (myofibrils, microvilli …)

Macromolecular complexes (ATPase, replisome, proteosome…)

Proteins, nucleic acids, carbohydrates, lipids (enzymes, DNA/RNA, polysaccharides, phospholipids…)

Amino acids, nucleotides, small sugars, fatty acids

Inorganic molecules, water, ions

(How is this organization achieved? Expenditure of energy!)

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hierarchy of biologically relevant time scales
Hierarchy of Biologically Relevant Time Scales

Dynamics on scales of:

  • Molecules
  • Biochemical reactions
  • Cells
  • Organisms
  • Evolution

ranging from femtoseconds

to billions of years!

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e coli as the standard clock
E. coli as the standard clock

Organismal and

cellular time scales

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e coli as the standard clock cont d
E. coli as the standard clock, cont’d

Subcellular time scales

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central dogma of molecular biology
Central Dogma of Molecular Biology

DNA

(template for DNA, RNA)

RNA

(mRNA: template for proteins)

Protein

Biochemical networks

(computing language of cell)

Timing the machines of the central dogma: Homework!

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amendments some examples
Amendments! Some examples…
  • Cell’s heritable characteristics are not solely determined by DNA; rather, a cell’s entire state (protein content) determines fate of descendants (eg. differentiation, transmission of pathology through prions,…)
  • RNA editing between mRNA synthesis and translation
  • Post-translational modification; chaperones and proteases

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dna rna building blocks
DNA/RNA Building Blocks

DNA/RNA are nucleic acids consisting of nucleotides (base+sugar+phosphate) subunits.

DNA: deoxyribose (sugar) RNA: ribose (sugar)

ATGC (bases) AUGC (bases)

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dna assembly
DNA Assembly

covalent bonding

hydrogen bonding

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3d structure
3D Structure

DNA

RNA

  • Base pairing yields double helix in DNA
  • Single helix and variety of folded structures in RNA

Discovery of DNA structure and function through combined efforts of chemists (Franklin), biologists (Watson and Wilkins) and physicists (Crick)!

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