Introduction to Biology

Molecules and Cells

Chapter 6 - Cells 

Cells are Tiny - Using Magnification

There are many things in the world that our eyes just aren't built to see:  things too far away, or too small, are beyond our ability to observe without some sort of devices to help.  Just as the telescope was a critical device for astronomers, the invention and development of the microscope was critically important to the progress of biology.

Although magnifying spectacles (glasses, sort of) had been in widespread use since the 1300s, the use of lenses to see very tiny objects was a slowly-developing technology.  First of all, the tinier an object is, the less light reflects off it or passes through it, and seeing anything really tiny requires a decent illumination system - you've got to get a lot of light on it.  Secondly, magnifying lenses used in early microscopes were made of glass that was not particularly even or clear, and tended to split light into colors like a prism, which affected the resolution limits of the lenses.  Resolution can be thought of as how clear a focus you can get;  technically, it is the limit at which two tiny objects which are close together stop looking separate.  The resolution of early microscopes was very limited by the glass used in the lenses.

Resolution in digital cameras.

A slideshow of particularly beautiful microscopic images.

Some important work was done with early microscopes, although for a long time they were really more of a toy than a scientific instrument.  Like telescopes that were being developed through that same period, many early microscopes used lenses in sequence (making them multi-lens or compound microscopes) to magnify an image.  In 1660, Italian Marcello Malpighi was able to use a microscope to see blood capillaries in the tail of a fish, providing powerful supporting evidence that blood circulates in the body (prior to this, since no one knew of how blood runs from arteries through too-tiny-to-see capillaries to veins and back, it was thought that the blood flow was one-way from production in the intestines to consumption in the body tissues).  In 1665, Englishman Robert Hooke found that cork was full of tiny chambers, which he called cells (there were no actual cells as they are now known in the dead cork, but the term did come from his label).  In the 1670s, Dutchman Antony van Leeuwenhoek, using a special, especially pure, non-prisming single lens (a simple microscope) placed in a holder and held up very close to the eye, was the first person to write extensively about a world of tiny independent creatures, which he called animalcules, which seemed to exist all around but were too small to be seen by eye.  Imagine what an odd idea that must have been to the people of the day!

A history of the microscope.

 

Marcello Malpighi.

 

Robert Hooke.

 

Antony van Leeuwenhoek.

 

Animalcule drawings.

It wasn't until the 1800s, through a interesting development period that included instances of thievery, plagiarism and questionable patent ethics, that many of the distortions of the lenses were corrected.  With the technological limitations for microscopes mostly solved, by the end of that century microscopes had begun to hit resolution limits set by physics:  to oversimplify, light beams themselves have a physical size, and when a gap is at or below about 0.2 micrometers the light itself can no longer fit through that gap - you can't see the gap, just a smudgy blob where the light has been blocked.  Objects below that size just could not be resolved as long as light was used in the imaging system.  Light microscopes (called that because they use light as an imaging system) would always remain useful, but most of the objects discussed in the next section on cell structures were invisible to them.  Although there have been some recent techniques in improving light microscopes' abilities, they are still limited.

Through the middle of the 1900s, a new system was developed that could use an electron system, an adjustable beam much smaller than visible light beams.  Electron beams can be narrowed to below the size of atoms producing incredibly good resolution.  The beam is focused with magnets and the final image converted to light in a way similar to how television screens work.  Recent versions of electron microscopes have been used to produce images of molecules and atoms.  Electron microscopes are more expensive and complicated than light microscopes, and the beam needs to travel through a vacuum to avoid scattering off air atoms.  They are very useful in research but not practical to use in classroom teaching labs any time soon.

Basics of light microscopes.

New advances in light microscopes.

A video showing how an electron microscope works.

 

Image of some interacting molecules.

A microscope for seeing atoms.
 

Picture of how microscopes are set up.

 

EM innards.

There are two basic microscope set-ups that affect the type of specimen that can be viewed and what the final image looks like;  both light and electron microscopes can be set up these two ways.   In a typical laboratory class microscope, light must pass through a specimen to reach the eyes of the viewer;  this set-up is an example of a transmission microscope.  For a specimen to be useful in a transmission 'scope, the beam needs to be able to pass through it and reveal its internal details, so it either has to be thin and semi-transparent, or sliced very thin into sections.  Objects are embedded in a material that will hold them together (commonly wax for light microscopy, plastic for electron microscopy) and then thinly sliced.  The ability to translate the two-dimensional information of sections into three-dimensional concepts is important in microscopy.  Specimens may then need to be stained, colored or darkened with special dyes, to produce clear details.  Colored dyes are used in light microscopy (the use of microscopes is called "microscopy"), while electron microscope stains have heavy metals in them  (the images are black-and-white, so the stain just needs to produce variations in electron absorption). 

The other set-up involves reflecting the beam off the surface of the specimen, which creates a much more three-dimensional image.  This is done by scanning microscopes, named for the necessity in the electron version of scanning the surface with the electron beam.  A dissecting microscope is a type of scanning 'scope.

An article showing (down a ways) stained sections of a transplanted bit of kidney.
 

Basic technique for preparing specimens, mostly for pathology analysis.
 

A typical section of a (slightly broken) cell seen with an electron microscope.
 

Scanning electron micrograph of an insect head.
 

A penny seen through a dissecting microscope.

In 1838, two scientists whose research centered on the microscopic inspection of living things proposed the Cell Theory.  Matthias Schleiden worked with plants and may have come up with most of the hypothesis that Theodor Schwann extended to animals.  The Cell Theory said:

• Everything alive is made up of at least one cell.

• Cells can only be made from existing, related cells.

• The smallest single thing that can be considered alive is a cell.

• This last one is sort of incorporated into the modern versions, but no longer listed as being part of the original:  Cells of all living things are more alike than different.

Cell theory.

Matthias Schleiden.

Theodor Schwann.

Basic Cell Types

There are two basic types of cells, prokaryotes and eukaryotes.  Prokaryote species can be found in Archaea and Monera, and are commonly called bacteria.  The rest of the Kingdoms contain eukaryotes.

Prokaryotes are always single cells;  they rarely even form colonial groups.  They have cell membranes and commonly have cell walls.  Compared to eukaryotes, prokaryotes have a simpler architecture:  internal chambers are rare.  This means that prokaryotes do not have a nucleus, or most of the cellular structures dealt with later in this chapter.   Prokaryotes have a single, loop-shaped chromosome in a specialized zone.  Many prokaryotes can make special small loops of DNA with one to a few genes on them.  These are called plasmids, and may be shared with other cells, changing their genetics - this is the closest that prokaryotes get to sexual reproduction.  For their "regular" reproduction, they copy the chromosome, hook each copy to the membrane, and divide the cell between the copies.

Eukaryotes have 2-ended chromosomes, usually in matched or homologous pairs;  they carry two copies of every gene.  Eukaryotes have many more special internal structures than prokaryotes, which will be the topic of the rest of the chapter.

Cells seem to have size limits:  bacteria seem to be close to the smallest a cell can be, and active cells seem to have a maximum allowable size.  No one knows why for sure, but the leading hypothesis is based on math.  If a spherical cell doubles in volume, it won't have double the surface, but much less - so all of the workings are doubled, but the way to get materials to and from those workings don't keep up.  Non-spherical cells aren't quite so restricted, but it is still thought that rather than get big, cells get more from groupings and specialization of members in the group, from multicellularity.

More on prokaryotes.
 

All about prokaryotes (bacteria).

 

Plasmid production.

A cartoon about plasmids and antibiotic resistance.

 

Picture of prokaryote cell reproduction.

 

A 2-ended eukaryote chromosome (2 copies still attached to each other, preparing for cell reproduction).

 

An explanation of the proposed math of size limits.

Cell Structures - Outside

Cells of any kind have a barrier layer around them, the cell membrane or plasma membrane, that somewhat isolates what's going on inside from the solutions around the cell (cells can only be fully active in a liquid environment):   this barrier is made by molecules that are lipids with a hydrophilic phosphate group where one of the hydrophobic fatty acids would normally be.  These phospholipid molecules, in water, naturally form a bilayer with the fatty acids turned toward each other, a waterproof layer, and the phosphates facing out at the water, allowing the membrane to interact with the solution around it.  The membrane is somewhat impermeable, meaning that many materials cannot just go through the barrier.  Since some things can move through, the membrane is semipermeable.

The membrane is not just phospholipids;  floating among those molecules are many types of proteins, some of which go through both layers, and some which float in just one side.  This concept of floating phospholipids with a pattern of proteins is called the fluid mosaic model of membrane.

The proteins can form pores, which will let small particles through;  channels, which may be more selective;  carriers, to move specific molecules through;  pumps to move materials in directions they wouldn't naturally go;  receptors, to allow the cell to interact with its surroundings;  markers, a recognition system for other cells;  and many other types of functioning proteins.

Image of a phospholipid molecule.
 

The bilayer (showing how cholesterol acts as a "spacer.")
 

Fluid mosaic membrane.
 

And in video.

 

Some embedded proteins.

Some cells have a secreted structure outside of the cell membrane that contributes to structure and can provide a bit of protection.  These cell walls, found in every Kingdom but the animals, can be made of many different materials.

Plant cell, showing the cell wall.

There are a few ways that materials can get into or out of a cell through the membrane.  If a material can pass through the membrane (the membrane is permeable to it), it moves naturally from where it is in higher concentration to where the concentration is lower.  For instance, as a cell uses oxygen, there is more oxygen on the outside moving in than on the inside headed out, so there is a net movement inside;  as cells produce carbon dioxide, the movement is outward for the same reason.  This movement is called diffusion.  Water molecules also diffuse, but then it's called osmosis.  Osmotic movement can actually generate a pressure - that's what moves water up short plants (eventually, the weight of the water counteracts the osmotic pressure or root pressure).  When materials diffuse through, they essentially move by themselves - this is called passive transport.  Some materials can only diffuse when special proteins let them through:  this is facilitated diffusion.  The fact that a cell can control and change what can and cannot move through it makes them selectively permeable.

What if a material must be moved through the membrane, going opposite to the way diffusion would move it?  This is active transport, and requires energy from the cell and specialized structures:  protein pumps to move small particles, or a system to surround materials with membrane and pull them in as membrane-lined chambers.  Going in, this is endocytosis;  going out, as often happens with secretions, it is exocytosis.

Video showing diffusion from single spot in an irregular container.
 

Facilitated diffusion video.

Osmotic pressure raises a water column.

 

Active transport.

 

Endocytosis, showing proteins involved.

 

Exocytosis (video).

Cells may have structures which project outward, including:

Pseudopods are an extension of the cell that has an inside similar to the cell's insides.  These structures can be used many ways.  Pseudopods can be used as slow, directional, crawling structures, as seen in an ameba or a white blood cell (or a cancer cell when it turns malignant).  They may also function as a thin extension to aid in floating, or to be used as a kind of tentacle.

Microvilli are many very thin extensions whose main purpose is to give the cell more surface area.  They are commonly found in cells that need to move a lot of material in or out, such as intestinal lining cells (absorbing nutrients) or in waste-removal systems like our kidneys.

Flagella and cilia are both thin projections with a core of mobile structures called microtubules.  They are used for swimming, or for moving materials past a stationary cell.  Although homologous, they have several differences:

Prokaryotes may have flagella, but they are not built like eukaryote flagella.

Pseudopod movement video.

 

Crawling ameba video.

 

Some pseudopod variations.

 

Microvilli.
 

Internal structure of flagella and cilia.

 

Flagella and cilia in action (video).

 

Cilia on respiratory surfaces (video).

 

Prokaryote vs eukaryote flagellum.

Cell Structures - Inside

Inside a eukaryote cell is a wide variety of chambers, channels, and clusters of cooperative molecules, doing for the cell jobs that in our bodies would be done by our organs.  These structures are called organelles.  Organelles float in a water-based fluid with many atoms, molecules, and even larger particles floating in it - this is called cytoplasm.  The cell is given physical structure by an assortment of proteins organized into a cytoskeleton.

Cytoskeleton is made up mostly of microfilaments, which hold things in place and are used to move things like pseudopods and microvilli, and microtubules, used for structure but also as conveyors of particles, movers of chromosomes during cell reproduction, and as the driving force in cilia and flagella.

A fairly famous animation video of cell activity.

A set of animation videos of the cell and cell structures.
 

Much more on cytoskeleton.

Organelles that are made up of cooperative clusters of molecules are generally found in prokaryotes as well.  Chromosomes, a cluster of DNA and proteins that keep it tightly packaged except when needed or being copied, are such a structure.  Another such structure are the ribosomes, a collection of RNA and protein molecules that act to take a gene code and translate it into a protein sequence.  A nucleolus, a molecular cluster inside the nucleus, is a storage place and processor of RNA.   These are just three examples of molecule cluster organelles.

How molecules interact in a chromosome.

Ribosome structure.

Nucleolus in a nucleus.

Many organelles have an internal membrane component.  Some are chambers with specialized, isolated chemistry in them, and some form channels and ways to subdivide parts of the cell.  Here is a list of a few types of membrane-based organelles:

Cell with organelles labeled.

Many membrane-based organelles fall into the category of just being simple membrane chambers where certain functions are performed.  Small chambers are vesicles, and include lysosomes, which contain digestive enzymes, and peroxisomes, where a lot of recycling of materials happens.  Larger chambers are called vacuoles, and include food vacuoles, pinched off from the outer membrane to get materials inside that couldn't otherwise enter, central vacuoles, which help reinforce support in multicelled plant systems, and contractile vacuoles, which pump out water when cells are exposed to dilute surroundings.

Lysosomes sometimes participate when a cell purposely kills itself, a process called apoptosis.  This is a very important process in multicelled systems:  failure to do this properly is a common underlying cause of cells becoming cancerous.

Lysosomes.

Many types of peroxisome.

Electron micrograph of a cell, with "fv" as food vacuoles.

Organelle table.

Apoptosis as a response to virus damage.

Golgi bodies (also called Golgi apparatus and Golgi complexes) are a collection of chambers, often roughly pyramidal in shape, where materials are processed to be secreted from the cell.  The top of Golgi bodies break off as vesicles, which carry the secretions to the membrane, fuse with the membrane, and dump the secretions out of the cell.

More on Golgi Apparatus.

Endoplasmic reticulum is a network of channels that is used to move materials from place to place with a bit more control than just letting them diffuse.  Smooth endoplasmic reticulum (SER) are just membrane channels;  rough endoplasmic reticulum (RER) has ribosomes stuck in the membranes, so newly-made proteins are released into the proper channel to go where they need to in the cell.

Endoplasmic reticulum.

ER often connects to the nucleus.

The nucleus actually has a double membrane, called the nuclear envelope, to isolate it from the rest of the cell.  This is a chamber where DNA is stored and processed, so it's where the chromosomes (when somewhat unwound, they are in the form called chromatin) and nucleoli are.

Nuclear structures and function.

There are at least two organelles that seem to have a weird history.  Although they are found inside eukaryote cells, these chambers have chemistry, structure, and genetics like certain prokaryote cells.  The endosymbiont theory proposes that in the distant past, a large cells took in  prokaryotes whose abilities made them more useful alive than digested, and the prokaryotes were protected by being in the larger cells.  Cells that were able to get "guests" into every offspring cell continued to have an advantage over competitors;  eventually, the guests became more of an organelle than independent agents.  Today, these organelles have small prokaryote-type chromosomes, but not enough genes to make more of themselves - they need to use genes from the nucleus for that.

History and evidence for the endosymbiont theory.

More evidence.

Endosymbiosis still happening - amebas with methane-processing bacteria inside them.

Almost every eukaryote cell contains an organelle called a mitochondrion.  Inside, the process of aerobic respiration allows a very efficient mobilization of the energy in glucose, using oxygen in the process and producing carbon dioxide and water.  The energy that was holding the carbons together in the glucose is largely moved to many ATP, the basic energy-supplying molecule of cells.

Mitochondrion and chloroplast.

Mitochondrial diseases:  modifying human embryos, producing 3-parent babies.

Eukaryote cells that perform photosynthesis do the process in organelles called chloroplasts.  These absorb light into chlorophyll molecules, freeing electrons that energize the reaction that captures carbon dioxide and water (freeing oxygen) and bonds the carbons together into the sugar glucose.

More on chloroplasts.

A whole library of cell structure images.

Go On to Next Chapter - Genetics and Reproduction

Introduction to Biology - Molecules & Cells.
For SCI-135.

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