Langmuir Trough
1917 Used to compress monolayers of molecules on the surface of a
given subphase(usually water), and can measure surface phenomena, or
deposit monolayers onto a solid substrate.
Gorter and Grendel
(1925)Evert Gorter and Fran�ois Grendel approached the discovery of
our present model of the plasma membrane structure as a lipid
bi-layer. They simply hypothesized that if the plasma membrane is a
bi-layer, then the surface area of the mono-layer of lipids
measured would be double the surface area of the plasma membrane. They
measured the total surface area of the plasma membrane of red blood
cells, and using Langmuir's method, they measured the area of the
mono-layer of lipids. In comparing the two, they calculated an
estimated ratio of 2:1 Mono-layer of lipids:Plasma
membrane. he two scientists proposed a structure for this
bi-layer, with the polarhydrophilic heads facing outwards towards the
aqueous environment and the hydrophobic tails facing inwards away from
the aqueous surroundings on both sides of the membrane
Davison and Danielli model
(1940)This theory declared that all biological membranes have a
"lipoid" center surrounded by mono-layers of lipid that are
covered by protein mono-layers. In short, their model was illustrated
as a "sandwich" of protein-lipid-protein. The
Davson-Danielli model threw new light on the understanding of cell
membranes, by stressing the important role played by proteins in
biological membranes.
JD Robertson
(1959) Basically, he suggested that all cellular membranes share a
similar underlying structure, the unit membrane. Using heavy metal
staining, Robertson's proposal also seemed to agree instantaneously
with the Davson-Danielli model. According to the trilaminar pattern of
the cellular membrane viewed by Robertson, he suggested that the
membranes consist of a lipid bi-layer covered on both surfaces with
thin sheets of proteins.
Dan Branton Freeze Fracture
...
Cell Membranes-Cell Fusion, Fluid Mosaic Model
Two cells of different origins can combine and their antibodies will
move evenly throughout the surface of the new membrane. proves
integral membrane proteins are mobile.
Cell Capping/Patching
Adding anti proteins will cause patching followed by capping
Frap Experiment
Membrane proteins are bleached, after time the bleached proteins
distrubte, but not completely evenly. Shows that 50% are mobile, other
half immobile. Cytoskeleton ad ECM limit the protein mobility.
RBC's
#NAME?
RBC Ghost
Outline of a cell but is unstainable, occurs in RBC's after they lose
their hemoglobin.
Elliptocytosis and Spherocytosis
Blood cells are elliptical instead of biconcave, can lead to anaemia.
Sphero is same with sphere.
Vernon Ingram
The Father of Molecular Medicine� for his research on Sickle Cell Anemia
Permeability of Pure Phospholipid Bilayer
Permeable to gas and small uncharged polar molecules, but not to
ions, or large molecules.
Phospholipids
Phospholipids are a class of lipids that are a major
component of all cell membranes. They can form lipid bilayers because
of their amphiphilic characteristic. The structure of the phospholipid
molecule generally consists of two hydrophobic fatty acid
"tails" and a hydrophilic "head" consisting of a
phosphategroup. The two components are joined together by a glycerol molecule.
phosphoglycerides
GLycerol Based phospholipids, main compnent of memrabes. PC and
Seline. Most common.
Sterols
Cholesterol
Give structure fluidity, are backbone of steroids.
Sphingolipids
In brain tissue, play major role in signal transduction and cell
recognition. High transmembrane resistance.
Flippase Experiment
Phospholipids can flip, cause by atp dependent enzymes. Caused by quencher.
Demyelination
Destabilizes mylein sheath cause remodeling, leads to diseases such
as multiple sclerosis.
Glycophorin
Classic dimer, integral membrane protein.
can be found in RBC membrane
Adherens Junctions
Cell adhesion molecule
Strength
Encircles cell, spots of attachment to ECM.
E-Cadherin Ca 2+ dependent
adherens junctions serve as a bridgeconnecting the actin
cytoskeleton of neighboring cells through direct interaction.
complexes that occur at cell�cell junctions in epithelial and
endothelial tissues,
Desmosomes
Desmosomes are one of the stronger cell-to-cell adhesion types and
are found in tissue that experience intense mechanical stress, such as
cardiac muscletissue, bladder tissue, gastrointestinal mucosa, and epithelia.
Pemphigus
in pemphigus, autoantibodies form against desmoglein. Desmoglein
forms the "glue" that attaches adjacent epidermalcells via
attachment points called desmosomes. When
autoantibodies attack desmogleins, the cells become separated from
each other and the epidermis becomes "unglued," a phenomenon
called acantholysis.
Pemphigus vulgaris (PV - ICD-10 L10.0) is the most
common form of the disorder and occurs when antibodies attack
Desmoglein 3. Sores often originate in the mouth, making
eating difficult and uncomfortable. Although pemphigus vulgaris may
occur at any age, it is most common among people between the ages of
40 and 60.
Pemphigus foliaceus (PF) is the least severe of the
three varieties. Desmoglein 1, the protein that is destroyed
by the autoantibody, is found in only the top dry layer of the skin.
PF is characterized by crusty sores that often begin on the scalp, and
may move to the chest, back, and face.
Tight Junctions
are multiprotein junctional complexes whose general function is to
prevent leakage of transported solutes and water and seals the
paracellular pathway. Tight junctions may also serve as leaky pathways
by forming selective channels for small cations, anions, or water.
Seperate between cell layers.
Best way to analyze is TEM(plastic thin sectioning)
Gap Junctions
Gap junctions are a specialized intercellular
connection between a multitude of animal cell-types.[1]
[2] [3] They directly connect the cytoplasm of
two cells, which allows various molecules, ions and electrical
impulses to directly pass through a regulated gate between cells.
One gap junction channel is composed of two connexons(or
hemichannels), which connect across the intercellular space.
Electrical junctions, fast, not site of learning.
Rectifying-1 way, non rectifying- 2 way
Neurochemical Synapse
endogenous chemicals that enable neurotransmission. It is a type of
chemical messenger which transmits signals across a chemical synapse,
such as a neuromuscular junction, from one neuron (nerve cell) to
another "target" neuron, muscle cell, or gland cell.
Slower, site of learning and memory
Ca2+ required for neurotransmitter release
Voltage gated calcium channels
Receptors
molecules (proteins) that interact with ligands and result in short
(cytoplasmic, transient) term and or (genomic, nuclear) long term
change in behavior.
Ligand
Molecules (natural or synthetic analog) that bind to receptors
resulting in a change in behavior.
Agonisis- turns is on
Antagonist- Turns is off
Signal Transduction
Enzymatic cascade that produces the L-R interaction into a change in
cell behavior.
Cell signaling types
Synaptic Neurochemical Paracrine
Neighboring cells Endocrine
Bloodstream Autocrine Self
Pharamones
Organism to organism
most ancient.
a secreted or excreted chemical factor that triggers a social
response in members of the same species. Pheromones are chemicals
capable of acting like hormones outside the body of the secreting
individual, to impact the behavior of the receiving individuals
Lipid Solubility
If ligand is membrane soluble
through membrane, recepetors in cytoplasm Used by
steroids
If not membrane soluble
Ion channel receptors receptor mediated
endocytosis
Familial Hypercholesterolemia (FH)
Class 1- LDL R not synstheisezed at all
Class 2- LDL is not properly transported from RER
Class 3- LDL doesn't bind to the receptor
Class 4- Clustering problem
Class 5- LDL-R not recycled properly
G- Proteins
also known as guanine nucleotide-binding proteins,
are a family of proteins that act as molecular switches inside cells,
and are involved in transmitting signals from a variety of stimuli
outside a cell to its interior.
Nanodisk
Synthetic model membrane system that places receptors in their native environment.
HER 2
Overamplification leads to malfunction in growth factors, and can
lead to breast cancer
Ras
Leads to signaling of growth factors. Mutations of this recepotr can
leas to cancer. roughly 50% of human cancers relate to this
Wnt
inactive rlowers b catenin, portesomal degradtion
Active raises b catenin
b catenin can affect growth of microtubules
TNF
The primary role of TNF is in the regulation of immune cells. TNF,
being an endogenous pyrogen, is able to induce fever, apoptotic cell
death, cachexia, inflammation and to inhibit tumorigenesis and viral
replication and respond to sepsis via IL1 & IL6 producing cells.
cAMP
Cyclic AMP is an important second messenger. It
forms, as shown, when the membrane enzyme adenylyl
cyclase is activated (as indicated, by the alpha subunit of a
G protein).
But an especially important protein activated by cyclic AMP is
protein kinase A, which goes on the phosphorylate
certain cellular proteins. The scheme below shows how cyclic AMP
activates protein kinase A.
Cholera Toxin
Prevents GTP hydrolysis.
Pertussis toxin precents relases of GDP.
Theophyline
Used in therapy for respiratory diseases.
Gi v Gs
Gi inhibits gs stimulates
Calcium/Cadodulin
Calcuim cofactor for select enzymes
Muscle conraction
E-cadherin
Neurotransmitter release
Cadherins (named for "calcium-dependent
adhesion") are a type of cell adhesion molecule (CAM) that is
important in the formation of adherens junctions to bind cells with
each other.Cadherins are a class of type-1
transmembrane proteins. They are dependent on calcium (Ca2
+) ions to function, hence their name.
Calmodulin
It is an intracellular target of the secondary messenger
Ca2+, and the binding of Ca2+ is required for
the activation of calmodulin. Once bound to Ca2+,
calmodulin acts as part of a calcium signal transduction pathway by
modifying its interactions with various target proteins such as
kinases or phosphatases
Calcium Ionophores � Ionomycin and A23187 � Potent Cell Death Drugs
Blood clots, Glutamate, Excess intracellular calcium = Neuronal cell death
NO
GAS
Blood pressure Penis erection - viagra
Can diffuse out of the cell it was generated from
Protein Destinations
Excreted/Secreted- insulin collagen EGF
Soluble in cytoplasm-Glycogen
Embedded in Plasma Membrane-LDL, GPCRS, RTK's
Organelles- lysosome, chloroplasts, mitochondria, nucleus, peroxisomes
Polyribosomes
Ribosomes & mRNA soluble(not membrane bound) in the cytoplasm
RER
Site of protein synthesis
Lamellar
Proteins secreted, integral proteins that stay in cell membrane,
Stay in ER or golgi, or go to lysomsomes.
Translocon
...
Golgi
Modifies proteins made in RER
Sorts and Sends to destinations
Synthesizes molecules that need to be secreted.
cis stack- closest to RER, accepts protein.
Protein Co translation
At ER membrane
Translocon is channel
SRP binf the signal sequence and connects it to the translocon.
GTP goes to GDP cleaves off SRP
Sognal Peptidase Cleaves signal sequence and releases folded protein
into ER lumen.
Signal sequence discovered by Milstein.
Translocation discovered by
Simon and Blobel
Ohms law
Bip
ATP dependent Chaperone protein
Keep proteins unfolded
Prevents slipping Located in RER
lumen Binds to nascent protein in post
translational translocation
UPR
Unfolded protein response
degrades unfolded proteins
tunicamycin stimulates UPR by blocking n linked glycosylation
Salubrinal supreses UPR
Type 1 Protein
Pass through ER 1 time
Stops transfer anchor sequnce
C end inside
Type 2 Protein
N end Inside
Tail Anchored Proteins
GET 1,2,3
GPI
ANchored proteins
Link but not by hydrophobic AA
Vesicular Traffic
...
RER Resdient protein
kDEL sequence
Bring them back to RER
pH sensitive
...
RER and Golgi
Dolichol phosphate
Initial glycosylation in RER
Found in RER N-linked
glycosylation