BME2106 Lecture+1.+Fundamentals+of+Molecules+and+Cells

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BME2106 - Introduction to

Cellular and Biomolecular


Engineering
Week 1

Dr. Bee Luan KHOO


blkhoo@um.cityu.edu.hk
Room no 6720

Department of Biomedical Engineering


BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Course Objectives
• Basics of cell and molecular biology, biochemistry,
and biotechnology.
• Provide you with a complete and concise overview
of bioscience, with a focus on its relationship to
biomedical engineering.
• Relationship between molecular structure and
function,
• The dynamic properties of organelles,
• The interaction between cells and the
microenvironment,
• The mechanisms that regulate cell activity,
• Practical applications of cell and molecular biology.

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Course layout

Contents
Week1: Fundamentals of Cell Biology (Tutorial CA 1A)
Week 2: Genes and Diseases (Tutorial CA 1B)
Week 3: Project preparation week - identify a human disease
of interest and the associated problem (no lecture)
Week 4: Proteins as Biomarkers (Tutorial CA 2A)
Week 5: Carbohydrates and Fatty Acids (Tutorial CA 2B)
Week 6: Mid-term test
Week 7: Microenvironment and Signalling (Tutorial CA 3)
Week 8: Metabolism (Tutorial CA 4A)
Week 9: Tissues (Tutorial CA 4B)
Week 10: Case study lecture (example for the project)
Week 11: Project presentation I
Week 12: Project presentation II
Week 13: Revision week/Recap

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Course Structure
Continuous Assessment: 70%
Midterm test 20%
Project 30%

Tutorials 20%

Examination: 30% (duration: 2 hours) (Date TBC)

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Mid-term test
MCQ
Closed book
2 hours
Materials up to Week 5

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Project
Individual

Aims:
Based on your understanding after Week 1,
[1] identify one physiological condition
[2] suggest why its pathological status is of importance
Upload the project title on CANVAS Pages by 28th January. The page will be made
available on 26th Jan (1st come 1st serve)

Based on your understanding after Weeks 1-9,


[3] suggest the mechanisms of this disease and how bioengineering approaches
can manage it

Submission of soft copy report and recorded presentation through CANVAS by


Week 11
Grading based on:
1) Written content (total 70%), reflecting these core components – problem
identified (10%), problem analysed (30%), solution proposed (30%);
2) Presentation (total 30%) (4+1 min per person)

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Tutorials
In-class (late submissions not accepted)
45 min each
Graded
Based on current lecture
Short answer
Open book
Online
Plagiarism report < 20%

20% total (2-5-5% each)

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
[1] Fundamentals of Cell
Biology

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
What is a micron? What is a nanometer?

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Perception of scale

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Why study Molecules and Cells?
- Lead us to fundamental understanding of life
- Understand important issues in medicine,
health, and nutrition
Has led to greater molecular understanding of diseases
such as diabetes, sickle cell anemia, and cystic fibrosis.
Next frontier: AIDS, cancer, Alzheimer’s Disease
- Advance biotechnology industries
Biotechnology is the application of biological cells, cell
components, and biological properties to technically and
industrially useful operations

1
BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong 2
[1A] All cells are the same…
right?

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Concepts: Cause and effect

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
But… Nature is not a direct 1
cause and 1 effect

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
The importance of biodiversity in Nature

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Complexity in Nature is a result of Biodiversity

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Diversity is essential, down to
the cellular level and more
Cellular diversity

Disease?

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
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BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
LIVING SYSTEMS APPEAR COMPLEX BUT
THERE IS AN UNDERLYING SIMPLICITY AND
ELEGANCE

- Most biological compounds are made of only SIX


elements: C, H, O, N, P, S What are these?

- Only 31 chemical elements occur naturally in plants


and animals

- All organisms have similar biochemical pathways.

- All organisms use the same genetic code.

- Limited number of molecular building blocks make


up larger macromolecules
BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
4 MAJOR CLASSES OF BIOMOLECULES SERVE AS
BUILDING BLOCKS FOR LARGER MACROMOLECULES:

1. Carbohydrates: e.g. glucose, fructose, sucrose - mainly used as sources of


cellular energy

2. Lipids: commonly known as fats


- organic compounds that are not very water soluble
- used as sources of cellular energy and - components of cell membranes

3. Amino Acids:
- 20 natural amino acids in total
- Used as building blocks for proteins

4. Nucleotides:
- 5 in total
- Used as building blocks for DNA and RNA precursors

5. OTHER:
- Vitamins: organic compounds necessary for proper growth and development
- Heme: Organometallic compound containing iron; important for transporting
oxygen in your blood stream. 11
ORGANISMS

2 basic classes of organisms


-Prokaryotes (e.g. E.coli)
-Eukaryotes

We will focus on eukaryotic cells and the biochemistry that


occurs in these cells.

Similar processes occur in ALL cells, including prokaryotes.

In fact, much of the biochemistry that we understand was


first uncovered in prokaryotic systems.

23
BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
[1B] Cell components

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
EUKARYOTES: Typical Eukaryotic Cell – Animal

a. Class includes plants, animals, fungi, protozoans, yeasts and some algaes.

b. Large cells (10-100 um in diameter). 10X bigger than prokaryotes.

c. Surrounded by a membrane called plasma membrane


i. Composed of lipids and proteins
ii. Serves as chemical barrier to the outside environment

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EUKARYOTES: Typical Eukaryotic Cell – Animal

d. Contain INTERNAL membranes and compartments. (Unique feature)


i. Compartments = organelles
ii.Organelles contain organized complexes of macromolecules that perform a
certain biological function.
iii. Most enzymes are compartmentalized
iv.Compartmentalization results in separation of biological function!!
.

26
EUKARYOTES: Typical Eukaryotic Cell – Animal

e. No cell wall in animal cells.

f. Plants, fungi, algae generally have a cell wall.

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1. Cytoplasm/cytosol
- Viscous aqueous environment (NOT free flowing)
- Contains small molecules, nutrients, salts, soluble proteins
- 20-30% of cytosol is protein – Very concentrated
- Highly organized environment **
- A major site of cellular metabolism (e.g. glycolysis)
- Contains cytoskeleton

28
BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Cytoskeleton
- 3-dimensional matrix made of protein fibers
-Functions to give cells shape, allows cells to move, guides
internal organelle movement.

29
BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Cytoskeleton

What is cytoskeleton?
The cytoskeleton is an intricate network of protein
filaments extending throughout the cytoplasm.
The cytoskeleton organizes the structures and
activities of the cell; support Large volume of
cytoplasm.

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Cytoskeleton

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Cytoskeleton

Highly complex!

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Cytoskeleton

Highly complex!
2. Cytoskeleton

The function of cytoskeleton


-Eukaryotic cells contain protein
fibers that are involved in

- Establishing cell shape


- Providing mechanical strength
- Cell movement
- Chromosome separation
- Intracellular transport of organelles
- Cell signaling

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Cytoskeleton

Structural Support
 Mechanical support
 Maintains shape
Fibers act like a geodesic dome to stabilize
and balance opposing forces
 Provides anchorage for organelles
 Dynamic
Dismantles in one spot and reassembles in
another to change cell shape

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Cytoskeleton

Structural Support - Cell motility

This involves both changes in cell location


and limited movements of parts of the cell.

The cytoskeleton interacts with motor proteins.


In cilia and flagella motor proteins pull components of the
cytoskeleton past each other. - Muscle cells

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Cytoskeleton

Structural Support - Cell motility


This involves both changes in cell location
and limited movements of parts of the cell.

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Cytoskeleton

Structural Support - Cell motility

1. Intermediate filaments

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Cytoskeleton

Structural Support - Cell motility


Intermediate filaments

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Cytoskeleton

Structural Support - Cell motility

Intermediate filaments
Filaments 10 nm wide => “intermediate”
Present in Animals
i.e. not Plants or Unicellular Organisms

Complex Gene Superfamily


70 in Human Genome

Specific Expression at Different Times and Places

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Intermediate filaments
1. Supports the structure of cells
--provide mechanical
strength to cells and
tissues

2. Forms a network throughout


the cytoplasm,
surrounding the nucleus and
extending out to cell peripher

3. Establishes a continuous
mechanical link between cells
within tissues (indirectly
connected); e.g. at
desmosomes
Intermediate filaments

1. Supports the structure of cells


--provide mechanical strength to cells and tissues

2. Forms a network throughout the cytoplasm,


surrounding the nucleus and extending out to cell periphery

3. Establishes a continuous mechanical link between cells


within tissues (indirectly connected); e.g. at desmosomes

4. Also found in the nucleus


--Nuclear lamina—strengthens the nuclear envelope.

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Intermediate filaments:
Mechanical support against mechanical stress

 Very stable. Little subunit exchange.

 Very strong. Filaments do not break


Different from:
 Microtubules: strong but brittle due to actin

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Intermediate filaments:
Mechanical support against mechanical stress

Microfilaments are often associated with myosin. They provide rigidity and
shape to the cell and facilitate cellular movements.
Intermediate filaments bear tension and anchor the nucleus and other
organelles in place

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Intermediate Filament
Potential Functions In Vivo

Mechanical Strength of Cytoplasm

Help a Layer of Epithelial Cells Resist Shear


Stress - Filaments Connect to Cell-cell Junctions

Hold Nucleus in Center of Cell

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Four Classes of Intermediate
filament

Keratin filaments: most diverse class,


- in epithelial cells;

Vimentent and vimentin-related filaments:


-in connective tissue cells, muscle cells, and glial
cells;

Neurofilaments: in nerve cells;

Nuclear lamins: in all animal cells.

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
2. Microtubule

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
MICROTUBULE
 Cross-section
• Hollow tube
• ~25 nm wide
the aggregation of tubulin in the form of microtubules

 Helical structure

 Polar
• Plus ends generally distal
• Minus ends generally proximal (at MTOC)

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Microtubules
1. Dynamic structure undergoing continual assembly and disassembly
2. Responsible for organization inside eukaryotic cells
Cell shape;
Cell movements, e.g., intracellular transport of organelles,
some forms of cell locomotion, separation of chromosomes
during mitosis

3. Grow in an organized manner


MICROTUBULE STRUCTURE &
ASSEMBLY

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Microtubules are organized from the
centrosome in animal cells
 Microtubules are ever-changing, with reactions constantly adding and
subtracting tubulin dimers at both ends of the filament (Figure 1). The rates of
change at either end are not balanced — one end grows more rapidly and is
called the plus end, whereas the other end is known as the minus end.

 Centrosome organizes the array of


microtubules radiating outward from it
through the
cytoplasm.
 Contain hundreds of ring-shaped
structure formed from γ-tubulin,
each serving as a nucleation site
(starting point) for the growth of
one microtubule
oDrives the assembly of
microtubules – concentration of
free αβ-tubulin is too
low to start the process
 Centrioles – made of a cylindrical
array of short microtubules
Microtubules in cell polarity

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
3. Micro (actin) filaments

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Actin filaments
 Polymers of the protein actin; present in
all eukaryotic cells;
 Thin and flexible;
 Actin and tubulin polymerize by similar
mechanisms;
 Many proteins bind to actin and modify its
properties.

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Some functions of actin filaments (microfilaments) are:

- to provide mechanical strength to the cell by forming a band under the


plasma membrane
- link transmembrane proteins to cytoplasmic proteins
- form contractile ring during cytokinesis in animal cells
- cytoplasmic streaming
- generate locomotion in cells such as white blood cells and amoeba
- interact with myosin to provide force of muscular contraction
Actin filaments allow animal cell
migration
 Cell cortex
• Actin filaments linked by actin-binding proteins into a meshwork
• forming a layer just beneath the plasma membrane
• giving the support for the outer surface of the cell and mechanical
strength

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Actin filaments allow animal cell
migration
 Lamellipodia
Thin, dense, sheet-like meshwork of actin
filaments with most of their plus ends
pointing to the plasma membrane;

Branched filaments formed with aids of


actin-related proteins (ARPs) – binding to
existing filaments and nucleate formation of
new filaments;

Continually being assembled at the leading


edge and disassembled further back,
pushing it forward

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Actin filaments allow animal cell
migration
 Filopodia
Thin, stiff protrusions at the leading edge of a crawling cell and elsewhere
on the surface;
Plus ends pointing outward; Usually 5-10 um long, can be 50 um long as
in axons;

 Contractile bundle
Interacting with motor proteins, myosins; May involve in
generating the pulling force for cell movement

BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
Actin binding proteins determine the behavior
of the actin filaments
3. Nucleus
- Site of most DNA and RNA synthesis
What is DNA? What is RNA?
- Storage of genetic information
- Bound by a double membrane
- Largest organelle in eukaryotic cells

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BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
4. Endoplasmic Reticulum (ER)
- Network of interconnected, closed, membrane-bounded vesicles
- Attached to cell and nuclear membrane
- Used for manufacturing, modification and transport of cellular materials
- Two types:

* Smooth ER = site of lipid synthesis


* Rough ER = site of protein synthesis via ribosomes
- Ribosomes are made up of RNA and proteins not bound by a membrane

62
BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong
5. Lysosomes What type of diseases are associated
- Internal sacs bound by a single membrane with lysosomes?
-Responsible for degrading cell components that have become obsolete for the cell or
organism.
- Internal pH ~5 (very acidic)
-Compartmentalization ESSENTIAL! Sequesters this biological activity from the rest
of the cell.
- Enzymes in lysosomes degrade polymers into their individual building blocks.

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6. Golgi Apparatus
- Flattened vesicles of lipid/protein/sugar
- Usually found near smooth ER and nucleus
-Involved in protein and fat processing and trafficking to other organelles (e.g. lysosomes,
plasma membranes)
- Distribution and shipping department for cell materials.

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7. Mitochondria
- Have double membrane (inner and outer)
- Place where most oxidative energy production occurs = “powerhouse” of the cell
- Form ATP – Convert oxygen and nutrients to energy
- Small, typically the size of a bacterium What is ATP?
- Contain a circular DNA molecule like that of bacteria (own genome)
- Because of the double membrane, size and presence of own genome,
- Mitochondria are believed to be descendants of a bacteria that was engulfed by a larger
cell billions of years ago 
- A cell can have over 1000 mitochondria!
- Depends on need for energy---muscle cells have a lot of mitochondria.

65
EUKARYOTIC CELL PARTS:

1
7
EUKARYOTIC CELL PARTS:

67
BME2106 - Introduction to Cellular and Biomolecular Engineering BME, City University of Hong Kong

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