Cell Biology Chapter 7

How the membranes define boundaries and serve as permeability barriers

Membranes have hydrophobic insides that are not permeable to hydrophilic molecules and ions. With this, it keeps things from outside of the cell out of the cell and regulates what comes into the cell

What do the different intracellular membranes of eukaryotic cells do generally

They serve to compartmentalize functions within eukaryotic cells

Membranes and proteins

Membranes have specific functions associated with them because the molecules and structures responsible for those functions- proteins, in most cases- are either embedded in or localized on membranes

Characterization of membranes with proteins

One of the most useful ways to characterize a specific membrane, in fact, is to describe the particular enzymes, transport proteins, receptors, and other molecules associated with it

Membrane (Bio) markers

Distinctive enzymes or proteins that are present in or on the plasma membrane or the membranes of particular organelles that help to identify them

Glucose phosphatase

A membrane-bound enzyme found in the endoplasmic reticulum, and its presence in, say preparation of mitochondria would demonstrate contamination with ER membranes

Structures of eukaryotic cells that involve membranes

Plasma membrane, nucleus, chloroplasts, mitochondria, endoplasmic reticulum (ER), secretory granules, and vacuoles

The five main functions of membranes

1. Define the boundaries of the cell and its organelles, 2. Serve as sites (loci centers) for specific proteins, especially enzymes and receptors; 3. Provide and regulate transport processes; 4. Contain protein receptors needed to detect external signals; and 5. Provide mechanisms for cell-to-cell contact, adhesion, and communication

Membranes and transportation of solute

The different transport proteins of membranes work to regulate what substances are taken up into various compartments. They also regulate the removal of the resulting wastes and products of various reactions

What regulates the transport of solutes in a cell

The proteins of the various membranes of the cell

Transport proteins in nerve cells

Nerve cells transmit electrical signals as Na+ and K+ ions are transported across the plasma membrane of neurons by specific ion channel proteins

Transport proteins in muscle cells

They move calcium (Ca+) ions across membranes to assist in muscle contraction.

Transport proteins in the chloroplast

The chloroplast membrane has a transporter specific for the phosphate ions needed internally for ATP synthesis

Transport proteins in the mitochondria

The mitochondria have transporters for intermediates involved in aerobic respiration

Aquaporin

Transport protein of water that can rapidly transport water molecules through membranes of kidney cells to facilitate urine production

The size limit of molecules that can be transported across membranes by transport proteins

molecules as large as proteins and RNA can be transferred across membranes by transport proteins

What forms the nuclear pore complexes in the nuclear envelope

Proteins form them

What goes through the pore complexes of the nuclear envelope

mRNA molecules and partially assembled ribosomes can move from the nucleus to the cytosol

What can the proteins that are synthesized on the endoplasmic reticulum or in the cytosol tdo

They can be imported into specific membrane-bounded organelles such as lysosomes, peroxisomes, or mitochondria via transport proteins

Proteins in the membranes of intracellular cesicles

They help facilitate the movement of molecules such as neurotransmitters either into the cell (endocytosis) or out of the cell (exocytosis)

How do cells receive information from their environment

Through the form of electrical or chemical signals that impinge on the outer surface of the cell

Signal transduction

The specific mechanisms used to transmit electrical and chemical signals from the outer surface of cells to the cell interior

Impinging signal molecules for signal transduction

Typically bind to receptor proteins on the outer surface of the plasma membrane which is then followed by specific chemical events on the inner surface of the membrane that often lead to changes in gene expression and cell function. Some, on the other hand, like estrogen are able to come within the cell themselves and interact with the proteins they need to interact with inside. Given that estrogen is non polar, it is able to do this

Concentration gradients in membranes

They transport molecules with no net charge

Electrochemical potential in membranes

Sum of its concentration gradient and the charge of gradient across the membrane facilitate the movement of ions

Simple diffusion in membranes

Works to transport water, oxygen, and alcohol

Facilitated diffusion in membranes

Works to transport polar molecules (e.g. sugars and amino acids) moved across the membrane by transport proteins

Facilitated water movement in membranes

Used by aquaporins in kidney cells

Active transport in membranes

Acts against the concentration gradient

Direct active transport

Requires ATP for 'uphill'

Indirect active transport

Of the solute to 'downhill'

Endocytosis

Brings molecules and ions into the cell through intracellular vesicles that facilitate the movement of the proteins involved

Exocytosis

Takes molecules outside of the cell. ER proteins of cytosolic proteins can be imported into the membrane bound organelles such as lysosomes, peroxisomes, and mitochondria

Chemical signal transduction

It is hormone based

Estrogen and chemical signal transduction

A polar steroid enters into target cell and interacts. It is a nonpolar molecule

Androgen and chemical signal transduction

it requires an androgen receptor

Progesterone and chemical signal transduction

Requires a progesterone receptor

Hormones and chemical signal transduction

Ligands help it to bind to receptors and activate series of internal chemical signals. Also requires a second messenger

Glucose and amino acid transporters

Muscle and liver cell membranes contain insulin receptors and can therefore respond to this hormone which helps cells take in glucose

Immune cell receptors

White blood cells have specific receptors to respond to chemical signals as they defend the body from microbial pathogens

Light-sensing receptors in plant cells

Many cells have light-sensing receptor proteins known as phytochrome that detect photons of light outside the cell and transmits a signal into the cell that alters gene expression and growth patterns

Cadherins

mediates specific cell-to-cell contacts. They have extracellular sequences of amino acids that bind calcium ions and stimulate adhesion between similar cells in a tissue +

The importance of cell to cell interaction

Most cells in multicellular organisms are in contact with other cells. During embryonic development, specific cell-to-cell contacts are critical

Bacteria and cadherins

Some pathogenic bacteria take advantage of adhesive membrane proteins to attach and invade intestinal cells and cause diseases

Examples of bacterial cells that attach to adhesive membrane proteins

Listeria and Shigella

Adhesive Junctions

Other types of membrane proteins in animal tissues form these junctions which cells together

Tight Junctions

These junctions form seals that block the passage of fluids between cells

Ankyrin

Membrane proteins that can be points of attachment to the cell cytoskeleton, lending rigidity to tissues

Gap junctions

Cells within a particular tissue often have direct cytoplasm sic connections that allow the exchange of at least some cellular components. This kind of intercellular communication is provided by these kind of junctions in animal cells

Plasmodesmata

A form of gap junction in plant cells

Fluid Mosaic Model

Is thought to be descriptive of all biological membranes, and envisions a membrane as two quite fluid layers of lipids, with proteins localized within and on the lipid layers and oriented in a specific manner concerning the two membrane surfaces. They have integral membrane proteins that are anchored to the hydrophobic interior fo the membrane by hydrophobic transmembrane segments while hydrophilic segments extend outward on one or both sides of the membrane. Peripheral membrane proteins are associated with the membrane surface by weak electrostatic forces.

Charles Overton

Observed plant root hairs and observed that lipid-soluble substances penetrate readily into cells, whereas water-soluble substances do not. He postulated that on the cell surface, there was a sort of lipid "coat" that explained the permeability observed. He even theorized that the 'coat' was a mixture of cholesterol and lecithin

Irving Langmuir

He studied the behavior of purified phospholipids by dissolving them in benzene and layering sample of the benzene-lipid solution onto a water surface. As the benzene evaporated, the molecules were left as a lipid film one molecule thick- that is, a "monolayer". He reasoned that phospholipids orient themselves on water such that their hydrophilic heads face the water and their hydrophobic tails protrude away from the water

E. Gorter and F. Grendel

They extracted lipids from a known number of erythrocytes (red blood cells) and used Langmuir's method to spread the lipids as a monolayer on a water surface. They found the area of the lipid film on the water to be about twice the estimated total surface of the erythrocyte. They then concluded that they erythrocyte plasma membrane consisted of not one, but two layers of lipids

The errors E. Gorter and F. Grendel made

They underestimated by about one-third both the surface area of the red blood cell and the amount of lipid present in its plasma membrane. Moreover, they did not take into account the significant portion of the erythrocyte membrane surface that is occupied by membrane-embedded proteins. These errors canceled each other out however making their conclusion correct

What did Grendel and Gorter conclude in hypothesizing a bilayer structure

They reasoned that it would be thermodynamically favorable for the nonpolar hydrocarbon chains of each layer to face inward, away from the aqueous milieu on either side of the membrane allowing the polar hydrophilic groups of each layer to face outward toward the aqueous environment on either side of the membrane

Dawson and Danielli

After Gorter and Grendel's discovery it became clear that a simple lipid bilayer could not explain all the properties of membranes such as those related to surface tension, solute permeability, and electrical resistance. With this Dawson and Danielli suggested that proteins are present in membranes in 1935. They proposed that biological membranes consist of lipid bilayers that are coated on both sides with thin sheets of protein

Dawson-Danielli model

A protein-lipid-protein "sandwich"

Modifications to the Dawson-Danielli model

A suggestion was made in 1954 that hydrophilic proteins might penetrate into the membrane in places to provide polar pores through an otherwise hydrophobic bilayer. These proteins could then account for permeability and resistivity properties of membranes that were not easily explained based on lipid bilayer alone. Specifically, the lipid interior accounted for the hydrophobic properties of membranes, and the protein components explained their hydrophilic properties

Robertson

With the discovery of the trilaminar structure of plasma membrane, he suggested that all cellular membranes share a common underlying structure, which he called a unit membrane. He suggested that the lightly stained space (between the two dark lines of the trilaminar pattern) contains the hydrophobic region of the lipid molecules which do not readily stain. Conversely, the two dark lines were thought to represent phospholipid head groups and the thin sheets of protein bound to the membrane surfaces, which appear dark because of their affinity for heavy metal stains

1950s and Membrane Advancement

With the advent of electron microscopy, cell biologists could finally verify the presence of a plasma membrane around each cell. They could also observe that most subcellular organelles are bounded by similar membranes. Membranes could be stained with osmium, which is a heavy metal, and then could be examined closely at high magnification. With this, they were found to have extensive regions of "railroad track" structure that appeared as two dark lines separated by a lightly stained central zone, with an overall thickness of 6-8 nm

Trilaminar

Three-layered staining pattern of plasma membranes with a railroad track structure that has two dark lines separated by a lightly stained central zone

Dawson-Danielli Model Shortcomings based on Size of the Membrane

Based on light microscopy, most membranes were reported to be about 6-8nm thick- and of this, the lipid bilayer accounted for about 4-5nm. That left only about 1-2nm of space on either surface of the bilayer for the membrane protein, a space that could at best accommodate a thin monolayer of protein consisting primarily of extended regions of B-sheet structure but as membrane proteins were isolated and studied, it became apparent that most of them were globular proteins with extensive regions of a helix. Such proteins have sizes and shapes inconsistent with the concept of thin sheets of protein on the two surfaces of the membrane, suggesting that they must protrude into the interior of the membrane

Dawson-Danielli Model Shortcoming Based on Membrane Distinctiveness

Depending on their source, membranes vary considerably in chemical composition and especially in the ratio of protein to lipid. With osmium staining, however, the membranes look essentially the same. As more membranes were studied, it became increasingly difficult to reconcile such enormous variations in protein content with the unit membrane model, because the width and appearance of the "rails" simply did not vary correspondingly

Protein/lipid ratio

Can be as high as 3 or more in some bacterial cells and as low as 0.23 for the myelin sheath that serves as a membranous electrical insulation around nerve axons

Dawson-Danielli Polar Head Shortcoming

When membranes were exposed to phospholipases, enzymes that degrade phospholipids by removing their head groups, 75% of the cell was degraded. It was believed that the polar heads were coated in a layer of protein that would protect it from such enzymes

Singer and Nicolson

Created the fluid mosaic model. This model envisions a membrane as a mosaic of proteins discontinuously embedded in, or at least attached to, a fluid lipid bilayer. They retained the basic lipid bilayer structure of earlier models but viewed membrane proteins in an entirely different way- not as thin sheets on the membrane surface, but as discrete globular entities that associate with the membrane on the basis of their relative affinities for the hydrophobic interior of the lipid bilayer

Integral Membrane Proteins

Amphipathic molecules that have hydrophobic regions that are embedded within the lipid bilayer in a way that makes these molecules difficult to remove from membranes. In other words, they are held in place by the affinity of hydrophobic segments of the protein for the hydrophobic interior of the lipid bilayer. Many have carbohydrate side chains attached to the hydrophilic segments on the outer membrane surface.

Peripheral Proteins

They are much more hydrophilic than integral membrane proteins and are therefore located on the surface of the membrane (they do not penetrate into the lipid bilayer) where they are linked non-covalently to the polar head groups of phospholipids and/or to the hydrophilic parts of other membrane proteins.

Lipid-anchored proteins

Not a part of the original fluid mosaic model are now recognized as a third class of membrane proteins. These are essentially hydrophilic proteins and therefore reside on membrane surfaces, but they are covalently attached to lipid molecules that are embedded within the bilayer

Fluid Nature of Plasma Membranes

Rather than being rigidly locked in place, most of the lipid components of a membrane are in constant motion, capable of lateral mobility (i.e. movement parallel to the membrane surface).

What does the fluidity of the plasma membrane allow membrane proteins to do

Many membrane proteins are also able to move laterally within the membrane, although some proteins are anchored to structural elements on one side of the membrane or the other and are therefore restricted in their mobility

Major Strength of the Fluid Mosaic Model in terms of Protein Arrangement

It readily explains most of the criticisms of the Dawson-Danielli model. For example, the concept of proteins partially embedded within the lipid bilayer accords well with the hydrophobic nature and globular structure of most membrane proteins in thin surface layers of unvarying thickness

Major Strength of the Fluid Mosaic Model in Terms of Protein/Lipid Ratios

The variability in the protein/lipid ratios of different membranes simply means that some membranes have relatively few proteins embedded within the lipid bilayer whereas other membranes have more such proteins.

Unwin and Henderson

They used electron microscopy to determine the three-dimensional structure of unfixed, crystallized bacteriorhodopsin and its orientation in the membrane. Their remarkable finding, reported in 1975, was that bacteriorhodopsin consists of a single peptide chain folded back and forth across the lipid bilayer several times. Each of
the seven transmembrane segments of the protein is a closely packed a-helix composed mainly of hydrophobic amino acids. Most membrane proteins have in their primary structure one or more hydrophobic sequences that span the lipid bilayer. These transmembrane segments anchor the protein to the membrane and hold it in proper alignment within the lipid bilayer

Transmembrane segments

Hydrophobic sequences of the primary structure of integral membrane proteins help to anchor the protein to the membrane and hold it in proper alignment within the lipid bilayer

Bacteriorhodopsin

The first membrane protein shown to possess the structural feature of transmembrane segments. It is a plasma membrane protein found in archaea where its presence allows cells to obtain energy from sunlight. To capture this solar energy, this protein has a molecule of retinal. Upon absorbing light energy, retinal triggers a conformational change in the protein that causes it to pump protons out of the cell. The resulting proton gradient across the plasma membrane can be used as a source of energy

Recent Developments on Membrane Structure

Recent developments emphasize the concept that membranes are not homogenous, freely mixing structures. Both lipids and proteins are ordered within membranes, and this ordering often occurs in dynamic microdomains known as lipid rafts. Most cellular processes involving membranes depend critically on specific structural complexes of lipids and proteins within the membrane. Cell signaling is an example of this process.

Membrane Lipids are considered what of the fluid mosaic model?

They are considered the "fluid" part of the model

Lipid Rafts

The ordering of the lipid and protein layers within plasma membranes occurs in these dynamic microdomains. They contain a lot of cholesterol, and sphingolipids (e.g. sphingomyelin) but less phosphatidylcholine. They also serve as the organizing centers for the assembly of signaling molecules.

What are the main classes of membrane lipids

Phospholipids, glycolipids, and sterols

Phospholipids in membranes

The most abundant lipid found in membranes. Membranes contain many different kinds of this lipid including both glycerol-based phosphoglycerides and sphingosine-based sphingolipids. The kinds of these lipids vary significantly among membranes from different sources

What are the most common phosphoglycerides

Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinstol

What are the most common sphingolipid?

Sphingomyelin

Glycolipids

They are formed by adding carbohydrate groups to lipids. Some are glycerol based, but most are derivatives of sphingosine and are therefore called glycosphingolipids.

What are the most common examples of glycosphingolipids

Cerebrosides and gangliosides

Cerebrosides

They are called neutral glycolipids because each molecule has a single uncharged sugar as its head group

Ganglioside

Always has an oligosaccharide head group that contains one or more negatively charged sialic acid residues that give the molecule a net negative charge. These lipids that are exposed on the surface of the plasma membrane also function as antigens recognized by antibodies in immune reactions

Where are cerebrosides and gangliosides more prominent in

The membranes of brain and nerve cells

Gangliosides and blood group interactions

The human ABO blood groups involve glycosphingolipids known as A antigen and B antigen that serve as specific cell surface markers of the different groups of red blood cells. Cells of blood type A have the A antigen, and cells of blood type B have the B antigen. Group AB blood cells have both antigen types, and group O blood cells have neither

Human diseases that are the result of the impaired metabolism of glycosphingolipids

Tay0sachs disease which is caused by the absence of a lysosomal enzyme, B-N-acteylhexosaminidase A which is responsible for one of the steps in ganglioside degradation. As a result of the genetic defect, gangliosides accumulate in the brain and other nervous tissue, leading to impaired nerve and brain function and eventually to paralysis, severe mental deterioration, and death

Sterols

Besides phospholipids and glycolipids, the membranes of most eukaryotic cells contain significant amounts of this lipids.

What is the main sterol in animal cell membranes

Cholesterol

Cholesterol

It is necessary for maintaining and stabilizing membranes in our bodies

What is the main sterol in plant cell membranes

Phytosterols. They also contain small amounts of cholesterol as well

Types of phytosterols

Campesterol, sitosterol, and stigmasterol

What is the main sterol in fungal cell membranes?

Ergosterol

Ergosterol

similar in structure to cholesterol but not found in humans. It is the target of antifungal medication such as nystain which selectively kills fungi but does not harm human cells since they lack this sterol

Sterols in bacterial cells

Sterols are not found in the membranes of most bacterial cells

Mycoplasma structural support

Sterols, though not found in the membranes of most bacterial species, are found in the membrane of this species, which lack a cell wall and presumably have sterols to add stability and strength to the membrane