Learning biology by numbers: Size and Geometry of cells, viruses and molecules; measurements in biology;

Cellular building blocks: four classes of macromolecules, nucleic acids and proteins are polymer languages
with different alphabets.

Making a Cell: Construction of Cells and Organism - Spatial organization, Temporal organization.
 Cell : The Unit of Life

• The smallest functional unit of life is cell,

discovered by Robert Hooke in 1665.

• A cell can independently perform all

necessary activities to sustain life. Hence
cell is the basic unit of life.

• There are two types of cells → plant cell

and animal cell.

• Cells have different organelles, each one

with a distinct function.

• Size of cells vary greatly

• Generally small and seen only with

microscope
Relative sizes of the cells

3
 Size and Geometry of cells

The standard cells. (A) A schematic bacterium revealing the characteristic size and components of E. coli. (B) A
budding yeast cell showing its characteristic size, its organelles, and various classes of molecules present within
it. (C) An adherent human cell. (adapted from Alberts B, Johnson A, Lewis J et al. [2015] Molecular Biology of the
Cell, 6th ed. Garland Science.)
Both plant and animal cells show diverse shapes such as –
Cell Organelles/Compartments -

Plasma membrane – Boundary, Protection and transport

Nucleus - hereditary data essential for multiplication and cell development.

Endoplasmic Reticulum & Golgi apparatus- Protein processing and Lipid biosynthesis

Mitochondria - Energy factories of cells

Lysosomes - digest undesirable materials present in the cell

Chloroplast (only Plant cells) – Photosynthesis

Ribosomes – Protein synthesis

Cell Theory
Cells were discovered in 1665 by Robert Hooke.

Early studies of cells were conducted by

- Mathias Schleiden (1838)
- Theodor Schwann (1839)

Schleiden and Schwann proposed the Cell Theory.

9
Cell Theory
Cell Theory
1. All organisms are composed of cells.
2. Cells are the smallest living things.
3. Cells arise only from pre-existing cells.

All cells today represent a continuous line of descent from the first
living cells.

10
Cell Theory
Microscopes are required to visualize cells.
Cell size is limited.
-As cell size increases, it takes longer for material to diffuse from the
cell membrane to the interior of the cell.

Light microscopes can resolve structures that are 200nm apart.

Electron microscopes can resolve structures that are 0.2nm apart.

11
Why are cells so small?
• Cells need to produce chemical energy (via metabolism) to survive and this
requires the exchange of materials with the environment
• The rate of metabolism of a cell is a function of its mass / volume (larger cells
need more energy to sustain essential functions)
• The rate of material exchange is a function of its surface area (large membrane
surface equates to more material movement)

• As a cell grows, volume (units3) increases faster than surface area (units2), leading
to a decreased SA:Vol ratio
• If metabolic rate exceeds the rate of exchange of vital materials and wastes (low
SA:Vol ratio), the cell will eventually die
• Hence growing cells tend to divide and remain small in order to maintain a high
SA:Vol ratio suitable for survival
•
Cell Theory
All cells have certain structures in common.

1. genetic material – in a nucleoid or nucleus

2. cytoplasm – a semifluid matrix
3. plasma membrane – a phospholipid bilayer

13
Cell
Theory

14
Prokaryotic Cells
Prokaryotic cells lack a membrane-bound nucleus.
-genetic material is present in the nucleoid

Two types of prokaryotes:

-archaea
-bacteria

15
Prokaryotic Cells
Prokaryotic cells possess
-genetic material in the nucleoid
-cytoplasm
-plasma membrane
-cell wall
-ribosomes
-no membrane-bound organelles

16
Prokaryotic Cells
Flagella
-present in some prokaryotic cells
-used for locomotion
-rotary motion propels the cell

17
Eukaryotic Cells
Eukaryotic cells
-possess a membrane-bound nucleus
-are more complex than prokaryotic cells
-compartmentalize many cellular functions within organelles and the
endomembrane system
-possess a cytoskeleton for support and to maintain cellular structure

18
Eukaryotic Cells

19
Eukaryotic Cells

20
Eukaryotic Cells
Nucleus
-stores the genetic material of the cell in the form of multiple, linear
chromosomes
-surrounded by a nuclear envelope composed of 2 phospholipid
bilayers
-in chromosomes – DNA is organized with proteins to form chromatin

21
Eukaryotic Cells

22
Eukaryotic Cells
Ribosomes
-the site of protein synthesis in the cell
-composed of ribosomal RNA and proteins
-found within the cytosol of the cytoplasm and attached to internal
membranes

23
Endomembrane System
Endomembrane system
-a series of membranes throughout the cytoplasm
-divides cell into compartments where different cellular functions
occur
1. endoplasmic reticulum
2. Golgi apparatus
3. lysosomes

24
Endomembrane System
Rough endoplasmic reticulum (RER)
-membranes that create a network of channels throughout the
cytoplasm
-attachment of ribosomes to the membrane gives a rough appearance
-synthesis of proteins to be secreted, sent to lysosomes or plasma
membrane

25
Endomembrane System
Smooth endoplasmic reticulum (SER)
-relatively few ribosomes attached
-functions:
-synthesis of membrane lipids
-calcium storage
-detoxification of foreign substances

26
Endomembrane System

27
Endomembrane System
Golgi apparatus
-flattened stacks of interconnected membranes
-packaging and distribution of materials to different parts of the cell
-synthesis of cell wall components

28
29
Endomembrane System
Lysosomes
-membrane bound vesicles containing digestive enzymes to break
down macromolecules
-destroy cells or foreign matter that the cell has engulfed by
phagocytosis

30
31
Endomembrane System
Microbodies
-membrane bound vesicles
-contain enzymes
-not part of the endomembrane system
-glyoxysomes in plants contain enzymes for converting fats to
carbohydrates
-peroxisomes contain oxidative enzymes and catalase

32
Endomembrane System
Vacuoles
-membrane-bound structures with various functions depending on
the cell type

There are different types of vacuoles:

-central vacuole in plant cells
-contractile vacuole of some protists
-vacuoles for storage

33
Mitochondria
Mitochondria
-organelles present in all types of eukaryotic cells
-contain oxidative metabolism enzymes for transferring the energy within
macromolecules to ATP
-found in all types of eukaryotic cells
-surrounded by 2 membranes
-smooth outer membrane
-folded inner membrane with layers called cristae
-matrix is within the inner membrane
-intermembrane space is located between the two membranes
-contain their own DNA

34
Mitochondria

35
 Chloroplasts of
Mitochondria of
Prokaryotes Eukaryotes Photosynthetic
Eukaryotic cells
eukaryotes
Multiple linear
1 single, circular chromosomes 1 single, circular 1 single, circular
DNA
chromosome compartmentalized in chromosome chromosome
a nucleus
Binary Fission Binary Fission Binary Fission
Replication Mitosis

Ribosomes "70 S" "80 S" "70 S" "70 S"

Found in the plasma Not found in the Found in the plasma Found in the
Electron Transport
membrane around plasma membrane membrane around plasma membrane
Chain
cell around cell mitochondrion around chloroplast
Size (approximate) ~1-10 microns ~50 - 500 microns ~1-10 microns ~1-10 microns
Anaerobic bacteria:
~3.8 Billion years
Appearance on Photosynt.bacteria: ~1.5 billion years ~1.5 billion years
~1.5 billion years ago
Earth ~3.2 Billion years ago ago
Aerobic bacteria:
~2.5 Billion years 36
Chloroplasts
Chloroplasts
-organelles present in cells of plants and some other eukaryotes
-contain chlorophyll for photosynthesis
-surrounded by 2 membranes
-thylakoids are membranous sacs within the inner membrane
-grana are stacks of thylakoids

37
Chloroplasts

38
Mitochondria & Chloroplasts
Endosymbiosis
-proposal that eukaryotic organelles evolved through a symbiotic
relationship
-one cell engulfed a second cell and a symbiotic relationship
developed
-mitochondria and chloroplasts are thought to have evolved this way

39
Mitochondria & Chloroplasts

Much evidence supports this endosymbiosis

theory.

Mitochondria and chloroplasts:

-have 2 membranes
-possess DNA and ribosomes
-are about the size of a prokaryotic cell
-divide by a process similar to bacteria

40
Cytoskeleton
Cytoskeleton
-network of protein fibers found in all eukaryotic cells
-supports the shape of the cell
-keeps organelles in fixed locations
-helps move materials within the cell

41
Cytoskeleton
Cytoskeleton fibers include
-actin filaments – responsible for cellular contractions, crawling,
“pinching”
-microtubules – provide organization to the cell and move materials
within the cell
-intermediate filaments – provide structural stability

42
Cytoskeleton

43
Cell Movement
Cell movement takes different forms.
-Crawling is accomplished via actin filaments and the protein myosin.
-Flagella undulate to move a cell.
-Cilia can be arranged in rows on the surface of a eukaryotic cell to
propel a cell forward.

44
Cell Movement
The cilia and flagella of eukaryotic cells have a similar structure:

9+2 structure: 9 pairs of microtubules surrounded by a 2 central

microtubules

Cilia are usually more numerous than flagella on a cell.

45
Cell
Movement

46
Extracellular Structures
Extracellular matrix (ECM)
-surrounds animal cells
-composed of glycoproteins and fibrous proteins such as collagen
-may be connected to the cytoplasm via integrin proteins present in
the plasma membrane

47
Extracellular Structures

48
49
 How cells are constructed?

▪ New cells are created from existing cells through a process referred to as the cell cycle. One
cell can make a copy of itself and form two new daughter cells.

▪ There are two major tasks that have to happen every cell cycle. First, cells have to make an
exact copy of their DNA. DNA is like the instruction manual for a cell. It encodes genes for
characteristics and dictates things like eye color and blood type.

▪ The second major task of every cell cycle is for the replicated chromosomes to be organized
and separated into opposite sides of the cell. This happens during mitosis, or M phase of the
cell cycle.

▪ The cell then grows longer, further separating those masses of chromosomes. The middle of
the cell then pinches off in a process known as cytokinesis, splitting the cell into two cells. A
new cell has been created and that completes the cell cycle.
 How cells build Organisms ?

Organizational control mechanism allows cells to form tissues and anatomical structures in the
developing embryo
Spatial and Temporal organization
▪ Individual-specific functional brain
networks can be elucidated in the
cerebellum

▪ Precision functional mapping of

individuals revealed that functional
networks in the cerebral cortex
exhibit measurable individual
specificity.
Cell Census
An order-of-magnitude census of the major
components of the three model cells
Importance of cell census
• Realistic physical picture of any biological phenomenon demands a precise, quantitative
understanding of the individual molecules involved and the distance between them
• You will find the cell interior is extremely crowded in contrast to the dilute and homogeneous
environment of the biochemical test tube.
• We will see that the mean spacing between protein molecules within a typical cell is less than
10 nm.
• This is extremely useful to estimate the rates of macromolecular synthesis during the cell
cycle.
E Coli: a model organism which has led to astounding discoveries
• Is easy to isolate present in human fecal matter
• E. coli is able to grow well in the presence of oxygen
• Easy to culture in lab, has high growth rate
• Genome has been sequenced 1997
• It carries plasmids extra-chromosomal DNA which can be manipulated
easily by molecular biology techniques.
• Molecular biology techniques are easy to apply for creation of mutants
• Often, we will have recourse to E. coli because of particular experiments
that have been performed on this organism.
• Further, even when we speak of experiments on other cells or organisms,
often E. coli will be behind the scenes coloring our thinking.
 Size of an E. coli cells and molecular composition
• E. coli. are made up of an array of different macromolecules as well as small molecules and
ions. To estimate the number of proteins in an E. coli cell
• We begin by noting that with its 1 fL volume, the mass of such a cell is roughly 1 pg, where
we have assumed that the density of the cell is that of water which is 1 g/mL.
Measurements reveal that the dry weight of the
• Cell is roughly 30 percent of its total and half of that mass is protein.
• As a result, the total protein mass within the cell is roughly 0.15 pg
• We can also estimate the number of carbon atoms in a bacterium on the grounds that
roughly half the dry mass comes from the carbon content of these cells, a figure that implies
1010 carbon atoms per cell
• Revealing the extent of crowding within a bacterium, we can estimate the number of
proteins by assuming a mean protein of 300 amino acids with each amino acid having a
characteristic mass of 100 Da.
• Using these rules of thumb, we find that the mean protein has a mass of 30,000 Da.
• Using the conversion factor that 1 Da 1.6 × 10−24 g, we have that our typical protein has a
mass of 5 × 10−20 g. The number of proteins per E. coli cell
 How big is an E. coli cell ?

▪ The size of a typical bacterium such as E.

coli serves as a convenient standard ruler
for characterizing length scales in molecular
and cell biology

▪ Diameter ≈1μm, a length of ≈2μm, and a

volume of ≈1μm3

▪ The shape can be approximated as a

spherocylinder—that is, a cylinder with
hemispherical caps.

▪ Inferences can vary with cell types under

various conditions. Relation between cell volume and growth rate. Using
microscopy and microfluidic devices, cell volume
can be measured at the single-cell level under
various conditions, confirming that the average cell
volume grows exponentially
with growth rate.
 =10-3Pa⋅sec

=147bp

1 Da = (mass of one carbon-12)/12

 E V ≈ 1μm3 = 1 fL
≈ 1pg
.Coli
m
E .Coli
≈ 1g / mL ≈ ρwater
ρ
E .Coli

1mol
molecule / 1 fL 6 × 1023 × 10−15 ≈ 2nM
1
= L Thermal energy scale (at 300K)

k B T = 4.14 × 10−21J = 4.14 pN ⋅ nm

AB  A + B  0.59kcal / mol

[A][B]
ΔG = k B T log d = k BT log ≈ k BT log10 −9= − 2.3 × 9kB T ≈ 20k BT
K [AB] −
≈ 20kBT (Kd = 1nM )[1molecule /
Typical protein-protein cell]
≈ 14kB T (K 3
d = 1μM )[10 molecules / cell]
interaction energy ≈ 7kBT (Kd = 1mM )[106 molecules / cell]
 (m
Water is 70 % of the cell mass E .Coli = 1pg)
Dry mass of the cell (30% of 1pg) = 0.3 pg

Half of the dry mass (=0.15 pg) = proteins

1
g = 1.6 × 10−24 g
1 Da = mass of a hydrogen atom = 6 × 1023
1 amino acid = 100 Da

average protein size = 300 a.a. → 30,000 Da

0.15 0.15 pg
Nprot= = ≈ 3, 000,
pg
30, −24
30, 000 × 1.6 × 10 000
⎧ 1N → 000Da g
membrane proteins mwater= 0.7 pg
⎪ prot
→
⎨ 3
⎪ 2
N prot → cytoplasmic proteins 0.7
N water= ≈2×
⎪ pg× 10−24 g /
18Da × (1.6
⎩ 1010
Da)
 6
There are proteins in cytoplasm
2 × 10
c = 2 × 106 / 1μm3
prot
⎛ ⎞
103 nm 3⎥ 1/ 3 = 500nm
d prot − prot
=c
−1/ 3
= ⎜( ) ( )1/ 3 ≈ 8nm
⎜ 2 × 106
⎝ 4 nm 4 nm
⎥
⎠

8 nm

Mean spacing between the macromolecules in

cell
~
size of macromolecules themselves

Cell is very crowded ... 28

Membrane
Surface area of E.Coli
A ≈ (2πR) × L ≈ 6μm2
E .Coli

E. coli has double (inner and

outer) membranes and each
membrane is made of
bilayer.

Half of the surface area is covered

with membrane proteins

4 × 0.5 × 6μm2
lipid
E ≈ ≈ 2 × 10 7
N .Coli 0.5nm2
29
Taking the molecular census to set criteria for the judgement

Measurement of protein census of E. Coli using 2D polyacrylamide gel electrophoresis

Experimental determination of biomolecular content

Large and negatively charged proteins

1.Protein mixture loaded at one end of
the gel and an electric field is applied
across the gel. (F=qE=ζv)
2.A charged detergent binding to proteins
is added. (charge of detergent ~ protein
size; q ~ R~v)

3. Proteins are stained using dye. Conc ~

Intensity of the spot.
4.Cut each spot, elute the proteins and
determine the size and amino acid
content using mass spectroscopy.
small and positively charged proteins
RIBOSOME
20% of the protein complement of a cell = ribosomal proteins
Ribosome (70S) = Large subunit + small subunit
Large subunit (50S) = 23S r-RNA + r-proteins
Small subunit (30S) = 16S r-RNA + r-proteins

S : Svedberg constant (sedimentation constant)

- A heavier particle sediments faster in the centrifugation, thus
have a larger S value.

m(1 − ρν )rω = ξ dr
2 dt
M (1 − ρν )D d log r
= ≡
RT ω 2 dt
S
⎧ r − RNA : 2/3 of the mass
ribosome (2.5MDa) ⎪
⎨⎪ r − protein : 1/3 of the mass
⎩
M
∴ N ribosome r − prot
=
0.2 × 0.15 pg
= 20, 000
mr − protein = 830, 000Da = m
r−
830, 000Da
M
r − protein
= 20% × M ≈ 19,
prot

protein
Conversion : Number ➯ Concentration ➯ Average
distance
* 1 molecule in a bacterium ~ 2 nM.

Example : Ribosome 1L = 10−3 m3

no. of ribosome = 19,000 (Table 2.1)
Concentration = 19,000/1fL ~ 32 μM
Average distance ~ 37 nm.
Cellular crowding and its implications
• The Cellular Interior Is Highly Crowded With Mean Spacings Between Molecules That Are
Comparable to Molecular Dimensions
• Increase in the effective concentration of macromolecules alters the rates and equilibrium
constants of their reactions
• Alters dissociation constants by favoring the association of macromolecules, such as when multiple
proteins come together to form protein complexes, or when DNA-binding proteins bind to their
targets in the genome
• Crowding may also affect enzyme reactions involving small molecules if the reaction involves a
large change in the shape of the enzyme.[10]
• The size of the crowding effect depends on both the molecular mass and shape of the molecule
involved,
 Cellular crowding and its implications
• the increase in the strength of interactions between proteins and DNA[5] is importance in processes such
as transcription and DNA replication
• involved in processes as diverse as the aggregation of hemoglobin in sickle-cell disease, and the responses
of cells to changes in their volume.[4]
• the crowding effect can accelerate the folding process,
• crowding can reduce the yield of correctly folded protein by increasing protein aggregation.[
• increase the effectiveness of chaperone proteins such as GroEL in the cell,[17]
• Crystallins fill the interior of the lens. These proteins have to remain stable and in solution for the lens to be
transparent; precipitation or aggregation of crystallins causes cataracts
• Crystallins are present in the lens at extremely high concentrations, over 500 mg/ml, and at these levels
crowding effects are very strong.

• The large crowding effect adds to the thermal stability of the crystallins, increasing their resistance
to denaturation
• This effect may partly explain the extraordinary resistance shown by the lens to damage caused by high
temperatures.[22]
• Crowding may also play a role in diseases that involve protein aggregation, such as sickle cell
anemia alzheimer's disease,
Biological Structures exist over
a huge range of scales
Hierarchy of spatial scales

Number of proteins in an E.coli cell

3,000,000
Number of ribosomes in an E.coli cell

20,000
Number of lipids in an E.coli cell

20,000,000
Size of genome in an E.coli cell

5,000,000 bp
 yeast cell : useful representative
to study eukaryotes

Tremendous diversity in living cells ...

Protist
Cells
Biological Structures exist over
a huge range of scales
Hierarchy of spatial scales
yeast cell : model system to
study a single eukaryote cell

Lyeast 5μm V = 4 π 2.5μm 3 ≈ 3

≈ 60VE
yeast
3
( )
.Coli
≈ 60 × N60 μm
E .Coli
Yeast protein
N protein

Yeast ≈ 2 × 0.5 × 80 μm2 ≈ 2 × 108

N lipid
0.5nm2 (
1.2 × 107 bp
) 7
N genome ~ 1.2 × 10 bp N nucleosome 
200bp /
= 60,
000
nucleosome
 Video resources
https://www.youtube.com/watch?v=URUJD5NEXC8

https://dnalc.cshl.edu/resources/3d/08-how-dna-is-packaged-advanced.html

https://www.youtube.com/watch?v=jOhNyVjkChM

43
VIRUSES

• A virus is an infectious microbe consisting

of a segment of nucleic acid (either DNA
or RNA) surrounded by a protein coat.

• A virus cannot replicate alone; instead, it

must infect cells and use components of
the host cell to make copies of itself.

• Often, a virus ends up killing the host cell

in the process, causing damage to the
host organism.

• Well-known examples of viruses causing

human disease include AIDS, COVID-19,
measles and smallpox.
▪ Viruses are much smaller than the cells they infect.

▪ They could pass through filters small enough to

remove pathogenic bacterial cells.

▪ These genomes can be DNA or RNA,

single-stranded or double-stranded (that is, ssDNA,
dsDNA, ssRNA, or dsRNA) with characteristic sizes
ranging from 103–106 bases

(A) Electron microscopy image of phi29 and T7

bacteriophages as revealed by electron microscopy. (B)
Schematic of the structure of a bacteriophage. (A,
adapted from Grimes S, Jardine PJ & Anderson D
[2002] Adv Virus Res 58:255–280.)
Cellular building blocks
▪ Cells of all organisms consist of four fundamental
macromolecular components: nucleic acids (including DNA
and RNA), proteins, lipids and glycans.

▪ From the construction, modification and interaction of these

components, the cell develops and functions.

▪ DNA and RNA are produced from the 8 nucleosides. Although

deoxyribose (d) and ribose (r) are saccharides, they are an
integral part of the energetically charged nucleoside building
blocks that are used to synthesize DNA and RNA.

▪ There are 20 natural amino acids used in the synthesis of

proteins.

▪ Glycans derive initially from 32, and possibly more,

saccharides used in the enzymatic process of glycosylation
and are often attached to proteins and lipids.

▪ Lipids are represented by 8 recently classified categories and

contain a large repertoire of hydrophobic and amphipathic
molecules.
The central dogma of Life