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L2_Cell types and subcellular structures

Title: Cell types and subcellular structures

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Lecture 2

4BBY1030 Cell Biology & Neuroscience

FoLSM/IoPPN Neuroscience Education

Dr Clemens

Kiecker Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Learning outcomes

By the end of this lecture you should be able to:

Explain the concept of the cell

Classify different types of cells: prokaryotes, eukaryotes, bacteria, archaea, fungi,

plants, animals

Outline the basic organisation of eukaryotic cells and give a brief description of the

major features and organelles, and the specialised cellular processes that take place

in them: plasma membrane, nucleus, rough and smooth endoplasmic reticulum,

Golgi apparatus, lysosomes and peroxisomes, mitochondria and chloroplasts,

cytosol, cytoskeleton Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Chapter 1

The concept of the cell

3Dr Clemens Kiecker Topic title: Cell types and subcellular structures

The cell theory

4

Our bodies are made up of approx. 37 trillion cells

Robert Hooke (1635-1703): microscope

Matthias Jakob Schleiden (1804-1881), Theodor Schwann

(1810-82), Rudolf Virchow (1821-1902):

Cell theory

  1. All living organisms are made up of one or more cells

  2. The cell is the basic unit of life

  3. Cells arise from existing cells by division Dr Clemens Kiecker Topic title: Cell types and subcellular structures

True or false?

All cells are surrounded by a plasma membrane

All cells are surrounded by a cell wall

All cells contain genetic material in the form of DNA

All cells contain DNA in a nucleus

All cells perform metabolism

All cells can move

5

Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Chapter 2

Types of cells

6Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Prokaryotes versus eukaryotes

Prokaryotes : no nucleus (Greek pro- karyon = before nucleus), always single-cellular

a) Bacteria (formerly eubacteria) including cyanobacteria (photosynthetic, formerly known as blue-green

algae)

b) Archaea (formerly archaebacteria): many species live in extreme environments (halophiles = high salt

concentrations, thermoacidophiles = hot sulfur springs etc.)

Eurkaryotes : nucleus (Greek eu- = true), single or multi-cellular

Plants (including algae)

Animals

Fungi (molds, yeasts, mushrooms)

Protozoans

7

Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Evolution of cells

8Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Chapter 3

9

Cellular organisation, organelles and

subcellular structures Dr Clemens Kiecker Topic title: Cell types and subcellular structures

The cell (plasma) membrane

Bilayer (double layer) of phospholipids, cholesterol

and embedded transmembrane proteins

Phospholipids = amphipathic = hydrophilic

phosphate group + hydrophobic lipid tails

Dynamic, lipid rafts

Four main roles:

  1. Barrier

  2. Communication

  3. Import and export

  4. Electrical capacitor

More on this in Lectures 6-8 and on 4BBY1013

10 Dr Clemens Kiecker Topic title: Cell types and subcellular structures

The cytoskeleton

Network of protein fibres:

  1. Actin filaments

  2. Intermediate filaments

  3. Microtubules

Main roles:

Maintenance of shape, stability

Adaptation of shape

Cell division

Motility

Movement of particles within cells

More on this in Lecture 4

11 Dr Clemens Kiecker Topic title: Cell types and subcellular structures

The cytoplasm (cytosol)

Aequeous solution of defined pH (approx. 7.2) and ion composition, but also contains:

A high concentration of proteins (20-30% metabolic enzymes, intracellular messengers

etc.)

tRNAs

Free ribosomes

Inclusion bodies (e.g. glycogen granules)

12 Dr Clemens Kiecker Topic title: Cell types and subcellular structures

The nucleus

13

Surrounded by two layers of membrane (two

lipid double layers) nuclear envelope

Contains nucleoplasm

Contains chromosomal DNA + packaging proteins

(histones) + gene regulatory proteins

Site of RNA synthesis and processing (RNA

splicing)

Nucleolus: site of ribosome synthesis (and signal

recognition particle), can capture gene

regulatory proteins (nucleolar detention)

More on this on 4BBY1013 and 4BBY1070 Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Endoplasmic reticulum (ER)

Network of interconnected membrane vesicles

(cisternae), continuous with the outer nuclear

membrane

Rough ER (rER): synthesis of secreted and

transmembrane proteins

More on this in Lecture 16 and on 4BBY1013

Smooth ER (sER): synthesis of lipids and steroid

hormones, detoxification (liver), release of

glucose from the liver

14

rER sER Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Golgi apparatus/complex

Stack of flattened membrane vesicles

Modification of proteins destined for secretion

and transmembrane proteins

rER cis Golgi trans Golgi secretory

vesicles

More on this in Lecture 14

15 Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Mitochondria

16

Often oval or sausage-shaped, 0.5-1 x 1-2 mm

Can make up to 25% of the cytoplasm

Double membrane: inner membrane folded into cristae

(high transmembrane protein content)

Contains circular DNA (mtDNA) and ribosomes in matrix

Alternative genetic code

Functions:

  1. Respiration/oxidative phosphorylation (electron transport

chain)

  1. Citric acid (Krebs) cycle

  2. Heat production

  3. Ca 2+ storage

  4. Programmed cell death (apoptosis)

Mitochondrial disorders: mutations in mtDNA (e.g. Kearns-

Sayre syndrome), defects in nuclear genes that encode

mitochondrial proteins (e.g. hereditary spastic paraplegia) Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Lysosomes

Membrane-bound organelles found in animal

cells

Degrade unwanted proteins and particles taken

up by the cell, and membranes and organelles

that are no longer needed

Acidic pH = 4.5-5 optimal environment for

degradative enzymes

Degradation of pathogens by macrophages

More on this in Lecture 17

17 Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Peroxisomes

Degrade fatty acids and toxic compounds

Fatty acid oxidation produces precursors for

biosynthetic pathways

Oxidation produces H 2O2 (corrosive)

The enzyme catalase neutralizes H 2O2:

2 H 2O2 2 H 2O + O 2

Detoxification of ethanol in the liver:

C2H5OH + H 2O2 CH 3CHO + 2 H 2O

18 Dr Clemens Kiecker Topic title: Cell types and subcellular structures

Recommended reading

Pollard, Earnshaw, Lippincott-Schwartz, Johnson, Pollard (2017) Cell Biology. 3 rd ed. Elsevier, PA.

Please note that the content of this book is broader than the learning outcomes of this module. Thus, do not

panic we do not expect you to study this book from the first to the last page. You should rather use it to

supplement your learning and as a resource if you have a question or if you find a particular topic interesting

and would like to learn a little bit more about it.

19

Thank you for your attention

[email protected]

Here goes the transcript from the video of the lecture: So this is the first subject lecture on the cell

biology and neuroscience module.

And what we're going to look at today are firstly

some classification and types of cells.

What does it actually mean.

What is a cell.

Where does this definition come from.

And then also looking at some of the features that

are characteristic of cells.

What I've been running here in the background whilst we

were waiting for everyone to come in, is a lovely

artist's simulation, giving you a little bit of an impression

of how it would look like if you were microscopically

small and could sit inside of a cell and see

what's going on there.

And this is this was prepared by colleagues at Harvard

University.

It's called the Inner Life of a cell, and you

can find it on YouTube.

It's a great thing to watch whilst you're doing your

morning yoga.

So it's very relaxing.

I strongly recommend it, but I'm going to stop this

for now and move on to my slides.

Right.

So what we're going to cover today, um, and what

you should be able to at the end of this

lecture is to get a bit of an idea of

what the, what this concept of the cell actually means.

What is it, what is what are the unifying characteristics

of the cell and we can classify different types of

cells, most importantly prokaryotes and eukaryotes.

And then there are various subtypes of them bacteria, fungi

plants animal animals.

And I'm going to come back to those in the

third lecture that we're going to have at 2:00, I

believe.

Um, and then I'm going to move on and talk

a little bit about the eukaryotic cells.

They're the more complex cell types.

Our cells are eukaryotic cells and they're characterised by um,

a division of labour.

So in a typical prokaryotic cell, everything is pretty much

in the same space.

Eukaryotic cells have developed so that different functions happen in

different compartments.

Oops sorry.

It looks like there's a timer on there.

Yeah.

Yeah.

So this division of labour is characteristic of eukaryotic cells.

And different parts of cellular functions happen in different places

which often are bound by membranes.

And these compartments within the cell are also known as

organelles.

And it is incredibly important for you that you know

these organelles, because in different cell types they are differently

represented.

But let's start by reflecting a little bit on what

this concept of the cell actually means.

Where does it where does it come from?

And I showed you this image in the introductory lecture

to the to the module.

And this is a very typical textbook image.

You probably have all seen something like this in your

A-levels, GCSEs, at whatever stage at school.

And that is a typical eukaryotic animal cell.

And if I say typical, this means typical in the

very sense of the word.

It is a stereotypical depiction of a cell Cells in

reality do not look anything like this.

Um, but this diagram really summarises the main features, and

some of the features are that the cell is surrounded

by membrane, it has a nucleus.

And we have these membrane bound organelles in the cytoplasm.

I did mention last week that our bodies are made

up of approximately 37 trillion trillions of these cells, and

none of them looks exactly like this.

They all look very different.

Some of them you probably wouldn't even recognise ourselves.

But when?

When did this concept of the cell emerge for the

first time?

So really, as as it's very often the case in

biology, the first time that people recognise that biological organisms

are made of cells came with a technical advance.

And that was the discovery of the microscope.

So this chap here, which was a an English physician,

Robert Hooke, invented the microscope in the 17th century, and

that for the first time enabled all sorts of scientists

to look at microscopically small structures, and in the following

century there were a number of researchers Schliemann, a German

physician, Theodor Schwann, an Austrian biologist and woodworker who was

a physician and ran one of the famous clinics in

Berlin in the 19th century.

They all used this microscope that Hooke had invented to

look at the microstructure of living organisms, often human tissues,

and particular Virchow.

Because he was an infectious biologist, he looked at the

the tissues of the of his patients, um, and and

analysed them at the microscopic level.

Schwann was a mostly a plant biologist.

So he looked at the structure of of plant tissues

under the microscope and surprisingly found that one unifying thing

is that all these tissues seem to be subdivided into

little compartments.

And Schwann was the first one who coined the term

cell for that because it looked a bit like a

sell, you know, almost like a prison cell, in particular

in plant cells.

If you've ever seen a microscopic image of a section

through an onion or the shoot of a leaf or

something like that, plant cells have this very regular, almost

rectangular, um, uh, shape.

And, and hence it makes sense to call themselves.

And before you panic, you do not need to remember

the names of these guys.

It's basically just to give you a bit of context.

Um, but but what all this research collectively came up

with is what we nowadays would call the cell theory.

And we can crystallise the cell theory in three main

statements.

The first one is all living organisms are made up

of one or more cells.

Whatever living organism on planet Earth you look at, it

will consist of cells, and that includes plants as well

as animals as well as unicellular organisms.

And that means that the cell is the basic unit

of life.

So any living organism you can split up further and

further until you end up with a cell.

It's pretty much the same like the atom in physics.

So you know any physical material you can split up.

The smallest unit is the atom.

In biology and in particular organismic biology, the cell is

the smallest unit of life.

And the and the third statement or postulate is that

cells always arise from existing cells by division.

So cells don't just miraculously materialise out of nothing, but

they can only form by division of cells.

Of course, some of you may think, well, at some

point there has to be the first cell on Earth,

right?

How did that arise?

And we're going to look at this a little bit

closer in the next lecture.

But any cells that are generated now, they don't they

don't develop de novo, but they basically come from cells

through division.

So before we're going to move on, I'm just going

to test your knowledge a little bit.

And a lot of us, you may remember from, um,

from school.

Um, I have a number of statements, and I just

want to show us, see a show of hands.

So if I say all cells are surrounded by a

plasma membrane, who thinks that is a true statement?

Good.

Who thinks it's a false statement?

Okay, good.

So you you remember some things from school.

That's excellent.

That is true because, um, indeed, every cell has a

plasma membrane.

All cells are surrounded by a cell wall.

Who thinks the statement is false?

Who thinks the statement is correct?

Okay.

Very good.

That's that's that's the correct answer again.

Um, not every cell is surrounded by a cell wall.

Some cells have cell walls.

Bacteria.

Many bacteria have cell walls that protect them and provide

stability.

Plant cells have cell walls and hence the the.

The bark of a tree, for example, tends to be

very hard because that is the.

These are the cell walls of dying cells that are

protecting a plant.

But not every cell has to have a cell wall.

Our neurones, for example, don't have cell walls.

All cells contain genetic material in the form of DNA.

Who thinks that's true?

Okay.

Few shy students lifting their hands.

And who thinks that's wrong?

Okay, a bit more.

A bit more cautious.

Um, I think your 4 or 5 colleagues that have

raised their hand, probably through you a little bit.

Well, it's actually both of you are right, because in

principle, every cell has to have genetic material.

I've said earlier, cells arise from other cells by division.

And something has to regulate how this perpetuation of the

form and shape of cells happens.

So there has to be genetic information and genetic material.

However, I've also told you last week that we have

some cells that get rid of their nuclei 30 to

40 million erythrocytes, red blood cells in our body don't

contain a nucleus anymore.

So they've kicked out their genetic material.

But that means they cannot perpetuate any further.

They can't divide again because they've lost this genetic information.

So I would say in this case, in this case,

I'm generous and either of you are giving the correct

answer.

Um, all cells contain DNA in a nucleus.

Well, that is definitely wrong because prokaryotes, these much simpler

cells that I mentioned earlier, don't have a nucleus.

We come to that in a second.

All cells perform metabolism.

Is that true or false.

Who thinks it's false.

Who thinks it's true?

Good.

Yes.

That's true.

Cells have to perform metabolism.

One of the characteristics of life is that there is

a constant turnover of energy and substances.

If something doesn't undergo metabolism, it's not alive.

Again, we have some cells that are very efficient at

reducing their metabolism to a minimum.

So some spores, for example, or fungi can persist for

thousands and thousands of years without much happening.

And then you put them in the right environment and

they start growing again.

So there's minimal metabolism there.

But in principle they still have metabolic enzymes and they're

still able to perform metabolism.

And finally, all cells can move who think that is

correct and who thinks that's wrong.

Yeah.

And again that's the correct answer.

We have cells that can move even within our body.

They're cells that can move.

Of course cells move with the bloodstream.

But there are cells that actively crawl to specific destinations.

But not all cells can move a brain cell a

new one in the brain, once it's been positioned in

a in a certain place is not going to.

Going to move around a lot.

Um, and in fact that's really important because if it

would move.

Then it would disrupt the network architecture of the brain.

So I've already mentioned that a couple of times.

We've got different types of cells.

And this typical textbook image that I showed you is

a depiction of a eukaryotic cell.

The word eukaryotic you comes from the from the Greek

for real.

So that's what we would call a real cell.

Um, or true down here.

Any multicellular organisms.

Is made of eukaryotic cell cells.

But we also have single celled organisms that are eukaryotes.

Now the other type of cell are prokaryotes.

And the essential difference between prokaryotes and eukaryotes is that

prokaryotes don't have a nucleus.

So you means to Carry out.

Carry on is the nucleus.

So a eukaryote is a cell with a true nucleus.

A prokaryote is a cell with no nucleus, or the

pro carry on is before the nucleus.

So it has an area somewhere in the cell that

looks a little bit like the nucleus where the where

the genetic information is concentrated.

But it's not packed up like in a in a

eukaryotic cell.

Eukaryotes I've mentioned this can be single or multicellular, but

prokaryotes are always single celled.

Um, and the prokaryotes include two major families.

Or that we should actually call them super families.

And they are bacteria.

And formerly they were known as Hugh bacteria.

And we've got the same syllable again.

So these are the real bacteria.

Um, and the second class or the second superfamily of

prokaryotes are the AAC and formerly AAC were called AAC

bacteria, But this has been revised, in particular with the

advent of genomic sequencing, because we know now that they

are so different genetically from bacteria that they belong to

a completely different branch of the tree of life.

Bacteria again form another a number of subfamilies, and those

include cyanobacteria, cyano.

The word cyan means blue or turquoise.

And these are bacteria that look blue because they perform

photosynthesis.

Formerly, these bacteria were sometimes also called blue green algae.

That is a wrong denomination because algae are plants, they

would be eukaryotes, and cyanobacteria are bacteria.

They don't have a nucleus, but they can undergo photosynthesis.

They can turn sunlight into energy.

And they are, I said previously were considered as part

of the of the bacterial superfamily.

But then they're very different from those.

And one of the characteristics of R.K. is that many

of their species have adapted to extreme environments.

Has anyone here ever been in the Yellowstone National Park

in the US?

No.

If you have a chance, then go.

You've got all these amazing hot springs there and they're

light up in beautiful different colours turquoise, red, purple and

so on.

Um, looks very inviting.

Don't jump into the hot springs.

They are normally almost boiling and full of things such

as sulphuric acid, so it wouldn't be very healthy to

do it to take a bath in them.

However, the, um, organisms that give these hot, hot springs

their colour are archaic, and they have adapted to these

extreme environments that can live in water with incredibly high

salt concentrations.

And these archaea would be called halo files.

Um, hallows is salt in Greek, and Phil always means

of fire means salt loving and thermal files, which can

persist very high temperatures, and a set of files which

can live at a really low pH and very acidic

concentrations, such as sulphuric acid.

So these are conditions in which the typical eukaryotic cell

would never survive, but have developed mechanisms to get around

that.

And that's quite interesting more recently for bioengineers, because that

means that the enzymes you find, for example, an archaeal

cell, are designed in a way that they can persist

high temperatures.

And that means if you have an enzyme that degrades

fat, you can put that in your washing powder.

And if you have a 60 degree wash, that will

still work, which doesn't happen with a normal eukaryotic cell.

So archaea have become really interesting as a source of,

um, um, all sorts of different substances that can persist

high temperatures, low pH, high soil concentrations and so on.

Now the eukaryotes.

Oh, there's a spelling mistake.

Eukaryote no are here.

So the eukaryotes include, um, fundamentally four classes of organisms.

The first ones are the plants, and that would include

algae.

I've mentioned before, eukaryotes can be single celled or multicellular.

So algae are single celled plants and trees, geraniums, roses,

whatever you find sitting around or bring to someone as

a present for who invites you for a dinner party.

These are all multicellular plants.

Animals, of course, including us.

We are animals.

Um, fungi.

And again, there are different types of fungi, different classes

of fungi.

We have moulds and yeasts as well as mushrooms.

And again, we have a distinction here.

Moulds and yeasts are single celled fungi.

Mushrooms are multicellular fungi.

Um.

and finally protozoans which are single celled eukaryotes.

And I'm going to show you an example for those

in the next lecture.

So.

Where do cells come from?

I've said earlier, at some point in the distant past,

the first cell must have developed in the primordial broth

on planet Earth.

And that's probably happened some three and a half to

4 billion years ago.

So our planet is an estimated 5 to 6 billion

years old.

Um, after the short period of 1 billion years, that's

when the first cells developed.

Um, and we can speculate later how they might have

looked at like.

But most likely there were prokaryotes because they were much

prokaryotes are much simpler and structure they don't have a

nucleus.

They are relatively easy to put together compared to a

eukaryotic cell.

So we start off with something that most likely looks

like a prokaryote.

And from there we can.

We have different branches.

One branch stays prokaryotic and develops into bacteria.

And these bacteria then include things such as the non

photosynthetic bacteria and the photosynthetic synthetic bacteria.

So these are the cyanobacteria that I mentioned earlier.

On the other side we have Aki.

So I've mentioned already they're sufficiently different genetically from bacteria

that they form their own branch of the tree of

life.

This is the tree of life here.

And the r k.

Um, yeah.

So they have this own branch, and many of them

now live in Yellowstone hot Springs and elsewhere.

This entire development happened over the space of some 1.5

billion years, probably.

And then finally we have the first ancestral eukaryotic cell

that develops.

And from there we have branches that lead to the

plants, the animals and the fungi and the protozoans.

So three major branches of the Tree of Life that

represent different classes of cells.

And in most of the module, so 95% of the

module, we are going to focus on eukaryotic cells because

we are made of eukaryotic cells.

You're all interested in what happens in the human body.

And that's what the focus of this this module is

about.

So in the next in the second half of the

lecture, I'm going to talk a little bit about how

eukaryotic cells are organised.

I'm going to mention some of these organelles that serve

cells to specialise or that that lead to division of

labour and other subcellular structures that you may be able

to find.

We've said earlier, and you've all said correctly, that one

of the hallmarks of cells is that they're also rounded

by a plasma membrane.

And so eukaryotic cells are also surrounded by a plasma

membrane.

And very schematically, again, this is an artist's impression of

a typical plasma membrane.

You can see all these little blue dots here.

These are the phosphate head groups of phospholipids, and the

brown bits are the tails of these phospholipids.

Phospholipids have a.

The phosphate head is water soluble.

The lipid tails are not water soluble.

So what happens is that phospholipids arrange in bilayers where

the the hydrophilic heads point outside and the lipophilic inside

points towards each other because it avoids water.

It's almost like when you take olive oil and shake

it with water, the oil separates from the water.

That's basically what happens here.

I'm not going into too much detail.

You're going to talk about this more in biochemistry.

In addition to this double layer or bilayer of phospholipids,

we also have other fat molecules, cholesterol for example.

You've all heard about cholesterol.

Um, it's often regarded as something that's bad for you

because if you have high levels of cholesterol, then it

can increase the risk of auto sclerosis and cardiovascular diseases.

But cholesterol also is really important factor because it is

the building block of many hormones that we use, and

cholesterol is found in membranes.

And again, that's biochemically important because if you stick cholesterol

molecules in between these phospholipid groups, the membrane becomes more,

um, becomes more, uh, the properties of the membrane change,

the flexibility of the membrane changes.

So cholesterol can act as a freeze protectant in membranes.

That keeps them flexible at low temperatures.

Um, the other thing that you can find embedded in

the membranes are proteins.

So here we have a protein that forms a spiral.

And one end one tail is sticking into the cytoplasm

down here.

The other tail sticks outside of the cell.

And our our cell membranes are studded with these transmembrane

proteins.

They have a number of different functions.

Some of them like this one here could for example

be a receptor.

So this is something that acts like an antenna that

binds a signalling factor.

And transducers a signal to the inside of the cell.

We're going to talk much more about this and one

of the later lectures on the module.

We have transmembrane proteins like this one that can form

channels.

And these channels are particularly important in neurones because the

electrical properties of the neuronal cell membrane is determined by

the opening and closing of channels that are permissive for

specific ions.

Again, you're going to hear much more about this in

some of the later lectures.

And you also have specialised structures which have different lipid

compositions which float in the rest of the membrane, almost

a little bit like an island.

And these are known as lipid rafts.

And they're very dynamic.

They become very fashionable to investigate and research in the

1990s because they are considered like specialised platforms where specific

transmembrane proteins are concentrated.

So, taken together, cell membranes perform four different functions.

They are, of course, a barrier because they separate the

outside of the cell from the inside, and the inside

is the cytoplasm.

And this barrier function is important because keeping differences is

crucial to maintain life.

And again really good example.

In case of nuance we need the barrier function because

the cell membrane is also an electrical barrier and it

allows the development of membrane potentials.

That's what's point four here.

So it acts as an electrical capacitor.

But although it's a barrier it also allows selectively for

communication between the outside and the inside.

So cell membranes are hubs or platforms for communication.

And they also are involved in import and export.

And again that's really important because cells depend on nutrients

and they need to be taken up from the outside

in order for the cell to survive.

And then once the cell has digested whatever they live

off air and there are some metabolic end products, then

they probably need to be expelled and released from the

cells in order to get get rid of them.

So import and export are also very important functions of

the cell membrane.

Now when we remove the cell membrane and look into

the cell, one of the first things that we would

see is the cytoskeleton.

And again this is something that often is neglected in

the textbook images of cells.

So you look at this textbook image of the cell

and you get the impression there's the membrane.

There are few organelles and everything else is a swimming

pool full of water.

That is not correct.

The inside of a cell is much more like a

gel.

It's quite viscous, and we have a network of cytoskeletal

elements that maintain the shape of the cell, but also

allow the cell to to change shape and to move.

There are three different classes of cytoskeleton, and these are

the smallest ones are the so-called actin Filaments.

The next bigger ones are the intermediate filaments and the

biggest ones are the microtubules.

They all perform different functions.

And we have a lecture.

The lecture for is dedicated on describing these different cytoskeletal

elements.

So Suba is going to tell you more about these

three classes of cytoskeletal fibres.

But collectively what the cytoskeleton does is it maintains the

shape and the stability of the cell, but at the

same time provides flexibility so cells can adapt to, to

change and can change their shape.

And the cytoskeleton is also involved in cell division, which

is arguably one of the most dramatic changes in shape

because the cell needs to be pulled apart into two

daughter cells.

It allows for motility.

I've said earlier, some of our cells crawl around actively,

so that is something that is enabled by the cytoskeleton.

And finally the inside, the the contents of the cell,

the organelles and other small particles can move around.

And this is something that is enabled by the cytoskeleton.

So cytoskeleton can also serve as train tracks for the

transport of cellular contents.

And again really important in neurones.

I told you last week, um, the axons of some

neurones in blue whales are 30m long, so it would

take way too long to wait for an organelle or

a mitochondrion that's produced in the cell body to be

transported to the to that axon.

If you would wait for that to happen by diffusion,

you would sit there for probably a million years.

But because we have cytoskeletal train tracks that run through

the axon, the mitochondrion can actively be transported from the

cell body to the um synaptic nerve ending.

And all this swims in the cytosol.

So this is now the sort of swimming pool like

stuff.

The liquid which is also known as cytoplasm or cytosol

because it contains salt.

Um, and the cytosol has a very, uh, has to

have a very defined pH and ion composition.

Cells can only function in a very narrow range of

ideal conditions.

And again I mentioned the r k earlier that that

can live in ponds with really high salt concentrations.

There inside still has to maintain a very narrow optimum

optimum of salt.

They are protected against the high concentrations outside because they

actively pump sold out of the out of the cytoplasm.

Sorry.

So the the cytoplasm of a typical cell would have

a slightly basic pH, something in the range of 7.2

very constant ion compositions.

But also it contains a whole number of other soluble

um components.

So for example, a very high concentration of soluble things

in the cytoplasm are actually proteins, Many metabolic enzymes are

found in the cytoplasm.

Glycolysis.

Have you had glycolysis in biochemistry already?

Glycolysis happens in the cytoplasm.

All these enzymes are found there but also intracellular messengers.

I've mentioned receptors earlier.

The receptor transducers a signal from the outside to the

inside.

But then you need to have secondary messengers that transduced

the signal from the receptor to the place in the

cell where that's needed.

And all these types of enzymes and proteins are found

in the cytoplasm.

You find tRNAs which are transfer RNAs that are involved

in protein synthesis.

Again, you're going to hear much more about this in

biochemistry.

You find, of course free ribosomes.

These are the factories that produce the proteins.

And you find things such as inclusion bodies.

So cells can store for example, glycogen um, for uh

for periods of deprivation where they, where they can very,

very quickly mobilise um glucose from glycogen and mobilise energy

through that.

But if in periods of abundance.

Glycogen is stored and this can appear as glycogen granules

in the cells.

And I know that all of this probably rings a

bell because you've heard about it before, but I think

it's a good idea to kind of bring you all

to the same level and remind you of the things

that you already may have forgotten from school.

Now, we've distinguished between prokaryotes and eukaryotes, and I've said

the defining feature of a eukaryote is the nucleus, because

you carry on means true nucleus.

And the nucleus is the usually the most prominent of

all cellular organelles.

And it is surrounded by a membrane.

So organelles are defined by usually they're surrounded by membranes.

The nucleus is surrounded not by one but by two

membranes.

And this double layer of membranes is also known as

the nuclear envelope.

What you can see here is part of a nucleus

in a scanning electron micrograph picture.

And you can see this is the nuclear envelope.

So we're looking onto the onto part of the nucleus.

And there are lots of little very regular shaped things

on there.

These are the so-called nuclear pores.

So the nucleus contains genetic information.

It of course needs to exchange this information with the

rest of the cell.

And that happens at these pores.

We're going to talk more about this in the lecture

on um protein intracellular protein transport.

The nucleus also contains a soluble solvent and water based

which is slightly different from the cytoplasm.

And that's known as the nuclear plasm.

And of course, the main thing that you find in

the nucleus is the chromosomes.

And chromosomes are DNA.

So the genetic information plus a whole bunch of proteins

that are specialised to wrap up the DNA um and

the and in eukaryotic cells these proteins are called histones.

They are evolutionarily some of the oldest proteins that are

known.

So that that was one of the things that has

appeared very early, hundreds of millions of years ago, when

eukaryotic cells developed.

And histones are essentially wrapping proteins.

So the DNA wraps themselves around the histones, and that

helps to compact the genome of the cell into the

small space, into the nucleus.

Because if you would unfold all the DNA that's within

one eukaryotic cell, it would kind of burst out.

It's much longer than the cell itself.

And then on top of that, you also have a

number of proteins that are involved in gene regulation.

And that's what for us as a molecular biologist are

the really interesting proteins, because they decide or they determine

whether a gene becomes switched on or switched off.

Um, many of in many cases, it's important that cells

switch on certain genes.

For example, if they if they fire up their metabolism

or if they respond to something.

But also sometimes genes are erroneously switched on or off,

and that can lead to things such as cancer.

And the nucleus, of course, is the site where RNA

is synthesised.

So once a gene becomes switched on, it is transcribed

into an RNA and the RNA is processed.

This is called RNA splicing and then exported from the

nucleus into the cytoplasm.

I'm going to gloss over this very quickly, because you're

going to cover this much more in genetics next semester.

And then finally there is a specialised area of the

nucleus which is known as the nucleolus, which in microscopic

images you often can see because it is slightly darker

in the practicals on the module.

When you do your histological staining reactions, you may actually

be able to see the nucleolus and cells, because it

tends to light up when you when you use, for

example, how much oxygen to stay in a cell, then

the nucleus often is visible as a dark blue dot

within the nucleus, and the nucleolus is a specialised area

of the nucleus where ribosomes are synthesised and particular the

RNAs of the ribosomes, but also the proteins, the signal

recognition particle which is part of the protein transport mechanisms.

Again more in another lecture.

And and another special function of the nucleus nucleolus, which

has only recently emerged, is that there seems to be

a mechanism that some genes are pulled from.

Chromosomes are pulled into the nucleolus to silence them.

So it is a there's a there's a higher order

mechanism of gene regulation where it depends on where a

piece of a chromosome is within the nucleus, where that

determines whether it becomes expressed or not.

So, you know, although the nucleus has been known for

a very long time, there's still research that reveals new

and unexpected things about this.

Um, uh, genetic powerhouse.

So if we move outwards from the nucleus, one of

the next things that you may see is the so-called

endoplasmic reticulum.

And that's shown in this cartoon here.

So the nucleus is indicated in purple.

I did mention earlier it's surrounded by a double membrane.

And this double membrane often is continuous with stacks of

membrane that you can see here in blue and then

in orange.

Now these stacks of membranes are the endoplasmic reticulum.

The blue stuff is the so-called rough endoplasmic reticulum or

Ras.

And it's called rough because it looks like it's studied

in an electron micrograph picture.

So this is a thin section a transmission electron micrograph

through a typical cell.

You can see these stacks of membranes.

And you can see if you've got good eyes.

You can see that these membranes are studded with little

dots almost like beads on a string.

And if you if you have really good eyes, you

may be able to see that these dots are always

only on one side of the endoplasmic reticulum membranes, and

because they're only studied to the outside, these dots are

ribosomes.

So they are protein producing factories.

And the rough endoplasmic reticulum contains lots of ribosomes because

it is the organelle where the cell produces secreted and

transmembrane proteins.

And this then is continuous with a less organised area

which is which doesn't have ribosomes.

And that's the so-called smooth and endoplasmic reticulum.

The thing to keep in mind is that these membrane

vesicles, flat membrane vesicles, they're almost stacked.

Think think about like a stack of pancakes that's a

bit hard looks like.

And these stacks of membranes tend to be interconnected.

So that's shown in this 3D image here.

If you look at electron micrographs you often just see

it looks like they're all separate, but they are usually

connected by small, um, bridges.

So the smooth endoplasmic reticulum in the electron microscope looks

less organised and it doesn't have any any ribosomes.

Now what's the function of the smooth endoplasmic reticulum.

This is where the cell synthesises lipids and steroid hormones.

So that is where cholesterol is modified and changed chemically

changed into many different types of hormones.

It also is involved in detoxification in particular in the

liver.

So a liver cell a typical liver liver cell has

huge amounts of smooth endoplasmic reticulum because that's where they

remove toxins from the from the bloodstream.

And finally it is also involved in releasing glucose from

the liver.

And when glucose needs to be enriched in the bloodstream

to provide energy.

Now next further away from the nucleus, the next stack

of membranes is the so-called Golgi apparatus or Golgi complex.

And again this is an electron micrograph here.

So you can see a section through a cell.

All these little dots are ribosomes.

And we have another stack of membranes.

And that is the Golgi apparatus.

So again looks a bit like a stack of flat

membranes like stack of pancakes.

Um, and this is now where the proteins that have

been produced in the, in the rough endoplasmic reticulum become

modified.

Again, these are typically transmembrane proteins or secreted proteins.

They often need further modifications.

For example, they need to be some carbohydrates attached to

them, or they need to be cross-linked to become more

stable, or they need to be folded in a different

way.

Or this happens can happen in the Golgi apparatus.

So the typical pathway of a secreted protein is from

the rough endoplasmic reticulum through the Golgi apparatus to secrete

the secreted vesicles.

The bit of the Golgi that's closer to the area

is called the psychology, and the bit of the Golgi

apparatus that's further away from the area and closer to

the cell membrane is the so-called trans Golgi.

Um, the next organelle that you've, I presume you've heard

about before is the so-called mitochondria.

So mitochondria, not completely different from nuclei, are surrounded by

two membranes, not by one membrane.

And you can see a transmission electron micrograph of a

typical mitochondria.

And here mitochondria are often slightly roundish but often a

little bit elongated like a like a bean or an

egg or sausage shaped.

Typical size of a mitochondria is something in the range

of half a micrometre to one micrometre times 1 to

2 micrometers.

So this axis would be, say, half a micrometre wide.

This axis would be one micrometre wide.

Micrometre sounds very small, but in cellular terms it's fairly

it's fairly big.

So you can see mitochondria.

You don't necessarily need an electron microscope.

You can see micro mitochondria with good light microscopes, but

you can't see all the details and if you see

the details, you find that you have an outer membrane

and you have an inner membrane.

And this inner membrane is folded and it forms these

weird stacks of enfolded membrane.

These enfolded bits are also known as crystal.

Um, and they contain a huge amount of transmembrane proteins.

Um, and if you remember your A-level biology from school,

the main function of mitochondria is that they are the

power stations of the cell.

So they produce ATP, chemical energy and form of ATP

using the electron transport chain.

And the electron transport chain is is dependent on a

huge multi protein complex where electrons are pumped across the

membrane.

And that happens at these at these membranes.

Here mitochondria can't contain their own genetic code.

So they have a little bit of DNA in there.

that, um, pleasant in in their content matrix um and

become later to why this might be interesting or relevant

and because they contain their own genetic information.

There are some disorders that are due to mutations in

mitochondrial DNA.

So for example, Colonsay syndrome, which is a very rare

disorder but is due to mutations in mitochondrial DNA.

There are also defects in genes that are encoded in

the nucleus that affect the mitochondria.

So this means the genetic information in the mitochondria is

not sufficient to make all the proteins that are needed.

Here.

There is some import of proteins from the outside of

the cell, but in particular hereditary spastic paraplegia, which is

a form of um, uh, movement immobilisation disorder.

That is something that is caused by a defect in

a mitochondrial protein that is encoded in the nucleus.

And I've mentioned it.

The main function of mitochondria is to provide energy.

The process is called oxidative phosphorylation or respiration.

It depends on the electron transport chain.

Again we're not going to cover this anymore here because

that's for the biochemistry module to cover, but also bits

of the bits that connect glycolysis with respiration, such as

the citric acid or the Krebs cycle.

They also happen in mitochondria.

Mitochondria also can produce other forms of energy.

So not just ATP, not just chemical energy, but also

heat.

And in particular, babies have something in mostly concentrated in

the back which is known as brown fatty tissue, which

is a fatty tissue which is particularly rich in mitochondria.

And the role of mitochondria there is to produce body

heat, so it increases the heat of the body.

Mitochondria also store calcium.

So calcium is a really important factor because it's not

only a component of bones, but in cells.

It is a signalling factor.

And that means you can't have huge amounts of calcium

floating around in the cytoplasm, because then you would trigger

all sorts of different signalling reactions.

So it needs to be contained.

And calcium is typically contained in endoplasmic reticulum and in

mitochondria.

And finally mitochondria are crucially involved in a process that

is called programmed cell death.

Sounds grim, but it's actually a beneficial thing.

So it's programmed because there are situations where the body

needs to get rid of, um, specific cell types.

So, for example, in the immune system, an important way

of honing the immune system to external factors only and

to prevent attack of body, of structures of the body,

is that those immune cells that would attack the body

are eliminated by programmed cell death.

If that doesn't happen or it doesn't happen properly.

That can result in autoimmune disorders and allergies.

Um, and also if so, for example, the reason why

I don't have webbed fingers like amphibians or fish is

that during embryonic development, cells between the digits become eliminated

by programmed cell death.

So cell death can be a good thing for the

benefit of the of the organism and its mitochondria that

are crucially involved in that.

You're going to have an entire lecture dedicated to cell

death where this is going to be covered more.

Yes.

Thank you for asking.

Um, lysosomes.

So this is another organelle that you may see in

an electron micrograph here.

Um, this is again a cross section, a transmission electron

micrograph of a section through a typical eukaryotic cell.

Up here you can see a mitochondrion.

You know, now this is a mitochondrion because it has

a double membrane and you can see the folding of

a crystal sticking in it here.

So this mitochondrion is more elongated and more sausage shaped

than the last one that we saw.

But also this mitochondrion doesn't look particularly healthy.

It doesn't have these neat little stacks of the crystal.

It kind of seems to be falling apart.

But it's probably a bit older and tired.

And we have another organelle here which is the so-called

lysosome.

And that seems to nibble on the mitochondria.

So lysosomes are specialised membrane bound organelles that degrade unwanted

proteins, particles, even entire organelles such as this dysfunctional mitochondrion

there.

And basically their function is to dissolve these bits.

They are like a big digestive system within the cell.

And how do they do that?

Well, they use an acidic pH, um, that enables enzymes

within the lysosomes to perform this degradation.

So the content of a lysosome is much more acidic

than the content of the cytoplasm, which was pH 7.2.

The content of the lysosome typically is 4.5 to 5,

and that creates an optimal environment for digestive enzymes.

Now that can be bad because if lysosomes burst within

the cell, then all of a sudden the cell becomes

very acidic.

That's not good.

And it would probably cause cell death.

Um, but normally the lysosome is protected by a membrane.

And we are going to towards the end of the

module, we are going to have two lectures on, um,

on the immune system.

Now, one important type of immune cell in the blood

are so-called macrophages, which gobble up bacteria can gobble up

an entire bacteria or other cells or viruses.

And um, and these the way these macrophages do that

is they have huge lysosomes which basically internalise the bacterium

and then dissolve them in this acidic broth that they

have inside.

Um, and again, I've said earlier, one of the characteristics

of cellular organelles is that they're typically confined by membranes

and that cells compartmentalise their work.

They have a division of labour.

And that's exactly that's really nicely exemplified by lysosomes here,

because you need to have a separate compartment where you

have this low pH, which is different from the rest

of the cell.

That means the dangerous bit, the degradation can only happen

there.

And accidentally one of the decorative enzymes would escape into

the cytoplasm.

It wouldn't do any harm because it needs the low

pH in order to degrade any invaders.

Almost coming to the end.

So the last little organelle that I want to mention,

which is considerably smaller than nuclei and mitochondria and lysosomes,

are the so-called paroxysms.

And again, the clue is in the name here.

So per oxy there is there usually oxidative processes happening

here.

And again this is a good example where the cell

sets aside a compartment to do a specific job.

That wouldn't that shouldn't happen everywhere because it could be

destructive.

So oxidative processes happen predominantly in paroxysms.

And they do things such as degrading fatty acids and

toxic compounds.

So again this is an organelle that you would find

a lot in liver cells.

Um but it also fatty acid oxidation also produces precursors

for a number of different biosynthetic pathways.

And the first thing that happens one of the key

mediators of oxidative processes within cells is H2o2, which is

hydrogen peroxide and is also the main component in bleach.

So essentially paroxysms are the little domestic bottles that we

have in our cells to allow for these oxidative processes.

So so bleach that's the same stuff that you poured

on the toilet in order to disinfect it.

And there's an.

And of course, if you would have huge amounts of

bleeds in the rest of the bleach and the rest

of the cell, that would be deleterious because it would

it would attack and oxidise other components of the cell.

But fortunately, there's an enzyme which neutralises bleach and this

enzyme is known as catalase.

And that's found in these peroxide zones.

So the the H2o2 that's produced in oxidative processes within

paroxysms is it's um, degraded by what's called in chemistry,

a disproportionate reaction into water and oxygen.

Um, but the same types of reactions involving oxidation, um,

also help with detoxification, for example, of alcohol or the

the correct chemical name here is ethanol.

So ethanol is what we have beer, wine, vodka in

different percentage percentages.

And that is detoxified in paroxysms in the liver.

This is the chemical formula of ethanol.

And if you oxidise ethanol with H2o2, you end up

with an acid, acetaldehyde, acetic aldehyde, and water.

Acetic aldehyde is less toxic than alcohol, and it can

be secreted from the bloodstream via the urine.

However, acidic aldehyde is has some toxicity, and it's actually

thought that what gives you the hangover after a big

night out is this stuff here in your bloodstream, so

that the degradation of alcohol leads to the stuff that

gives the hangover the next day?

Um, people that have low amounts of the enzymes that

are involved in this, um, tend to stay, um, drunk

for longer, but also tend to not have hangover hangovers

because they don't have they don't produce these, uh, um,

uh, Unpleasant chemicals.

And.

Yeah.

So this was a survey of the main interesting and

relevant organelles and substructures that you find in the cell.

All this is covered in this book.

And again, do not feel like you need to read

this from A to Z.

But if you found something really interesting and you want

to know a little bit more about the mitochondria, there's

probably an entire chapter in this book dedicated to it.

You don't have to read this for the exams, but

do read it if you haven't understood something, or if

you just found it interesting enough that you want to

know more about it.

I'm going to see you in a couple of hours

for lecture number three in this lecture Theatre.

Thank you.

Hello.

So in this world, I think.

We have to move.

Away from the linear.

Yeah.

Yeah.

It's a it's it's actually a Markov property.

So if you.

If you would go to a microscopic segment and you

want.

To know where there's a lifetime, you could put yourself

on a carpet and use an antibody against satellite, but

then you would see the results and then you would

like obviously you have your.

Husband for the journey.

I didn't I didn't get the generator by accident for

them to assume and things like that.

Okay.

All right.

Thank you.