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What is the plasma membrane?
a collection of proteins & other molecules embedded in the fluid matrix of the lipid bilayer
What is important about the α-helix of transmembrane protein?
it’s typically long enough to cross the bilayer
How do the polar peptide bond atoms bond with each other?
H-bonds
What is one way of creating pores across the membrane?
One or more α-helices can be used
Describe the general structure of a potassium channel
Amphipathic α helices interacting to form a channel through the cell membrane
Ion Channels
These proteins create pathways for specific ions (like sodium, potassium, calcium, and chloride) to move across the membrane.
Ion channel examples
voltage-gated ion channels and ligand-gated ion channels.
Aquaporins
Transmembrane proteins that facilitate the transport of water molecules across the membrane, ensuring water balance within the cell
Gated channels
These channels open and close in response to specific signals, regulating the passage of molecules.
Gated channel examples
neurotransmitter-gated channels in nerve cells open in response to chemical signals.
Gap Junction Proteins (Connexins)
These proteins form gap junctions between adjacent cells, allowing direct communication and the exchange of ions, small molecules, and signaling molecules.
Porins
Found in the outer membranes of bacteria, mitochondria, and chloroplasts, these are proteins that create channels for the passage of ions and small molecules
Proton Pump (Proton ATPase)
This transmembrane protein actively transports protons across the membrane, contributing to the establishment of proton gradients essential for processes like ATP synthesis.
Sodium-Potassium Pump (Sodium-Potassium ATPase)
This pump actively transports sodium ions out of the cell and potassium ions into the cell, maintaining the cell's electrochemical gradient.
Calcium Channels
These channels regulate the influx of calcium ions, which play crucial roles in various cellular processes such as muscle contraction and neurotransmitter release.
Selective permeability of phospholipid bilayer molecule transfer ease (easiest to hardest)
small nonpolar molecules
small uncharged polar molecules
large uncharged polar molecules
ions
What does cell permeability depend on?
– Molecules size (better to be small)
– Polarity (electric dipole moment)
– Charge (anion vs. cation; negative vs positive)
– Water vs. lipid solubility
Passive transport
Simple diffusion and facilitated transport
Simple diffusion
diffusion of small, nonpolar, hydrophobic molecules
– lipids
– HIGH → LOW concentration gradient
Facilitated diffusion
diffusion of small, polar, hydrophilic molecules through a protein channel
– HIGH → LOW concentration gradient
Active transport
– diffusion against concentration gradient LOW → HIGH
– uses a protein pump
– requires ATP
Functions of plasma membranes
Selective barrier: surround cells to hold enzymes and metabolics inside. cellular compartmentation surrounds organelles
Contain enzyme systems: energy metabolism
Contain transport systems: bring food molecules inside and maintain ion concentrations
Contains specific recognition sites: for hormones, other cells, etc.
Functions of membrane proteins
transport, enzymatic activity, signal transduction, cell-to-cell recognition, intercellular joining, attachment to cytoskeleton and ECM
Osmosis
(type of simple diffusion) the net flow or movement of solvent molecules through a semipermeable membrane through which solute molecules cannot pass. The solvents move from less concentrated solution to more concentrated.
T/F: water passage through the pores in membrane integral proteins (porins) depends on temperature
False
How is aquaporin high specificity achieved?
a channel diameter of 0.2 nm (not even H+ or OH- can pass through)
What is the first law of thermodynamics?
Energy is not created or destroyed, but can change form
Entropy
A measure of the degree of disorder of a system
How does glucose compare to CO2 and H2O?
Glucose is more organized, more potential energy, and less stable (less entropy)
Bulk transport
Movements of large solids (phagocytosis) or liquid (pinocytosis) molecules across the cell membrane using energy from respiration
Endocytosis
External large molecules enter the cell by forming an invagination in the cell membrane and eventually a vesicle surrounding these molecules; an active process, requires ATP
Exocytosis
Types of endocytosis
Phagocytosis
Pinocytosis
receptor-mediated endocytosis
Basic process of endocytosis
the cell membrane folds inward, forming a pocket around the target particle or particles
the pocket then pinches off with the help of specialized proteins, leaving the particle trapped in a newly created vesicle or vacuole inside the cell
Phagocytosis
a form of endocytosis in which large particles, such as cells or cellular debris, are transported into the cell. Cells ingest large particles into membrane-bound vesicles called phagosomes, which are then targeted by lysosomes for enzymatic degradation
Neutrophils
abundany in blood, quickly enter tissues, and phagocytize pathogens in acute inflammation
Macrophages
Closely related to monocytes in blood, longer-lived cells predominate in chronic inflammation. Also release some important inflammatory paracrine
Dendritic cells
phagocytosis in these cells is important for the elaboration of a specific immune response rather than for directly destroying the pathogens
B Lymphocytes
a small amount of phagocytosis in these cells is necessary…
Invasion mechanisms
some bacteria induce phagocytosis via zipper mechanism. Once phagocytosed, bacteria such as Listeria and shigella escape the phagosome and live within the host cytosol
Salmonella endocytosis
Salmonella destroys the microvilli of enterocytes and then invaginates into the cell, where they exist within a Salmonella-containing vacuole
How does induced phagocytosis occur?
SipA and SipC interact directly with actin
Host GEF mimetics SopE, SopE2, and SopB activate the host RhoGTP pathway, which induces actin polymerization
Following the successful endocytosis, SptP induces actin depolymerization and facilitates the recovery of the host cell
How do the vesicles of pinocytosis compare to phagocytosis?
They are smaller
Spontaneous endocytosis
bulk-phase endocytosis or pinocytosis; doesn’t need specific signals or stimuli.
Receptor-mediated endocytosis
highly-specific and well-controlled. form of endocytosis in which receptor proteins on the cell surface are used to capture a specific target molecule. The receptors, which are transmembrane proteins, cluster in regions of the plasma membrane known as coated pits.
Describe the process of receptor-mediated endocytosis
Receptors bind to specific target molecules → endocytosis is triggered → receptors and attached molecules are taken into the cell in a vesicle
Aspects of clathrin-coated vesicles
clathrin
adaptor protein
cargo complex: membrane + cargo receptor + cargo
Stages of exocytosis in secretory cells.
(a) Formation of vesicles
(b) vesicle "docking”
(c) the transformation of vesicles into fusion-competent vesicles ("priming")
(d) fusion.
What allows exocytosis that is primed to occur?
Calcium
Types of chemical signals
receptor-ligand interactions, signaling molecules, pathogen entry
Receptor-Mediated Endocytosis
Specific molecules or ligands bind to cell surface receptors
What does receptor-mediated endocytosis binding trigger?
receptor clustering and signals the cell to internalize the ligand-receptor complex
Example of receptor-mediated endocytosis
low-density lipoprotein (LDL) particles binding to LDL receptors.
Types of signaling molecules
neurotransmitters, hormones, and growth factors
What do neurons release?
neurotransmitters
What do neurotransmitters bind to, and what does this trigger?
receptors on neighboring cells, triggering endocytosis of neurotransmitter-receptor complexes.
What can hormones initiate?
endocytosis upon binding to their cell surface receptors.
What do growth factors bind to?
receptor tyrosine kinases (RTKs) on the cell surface
What does internalization of growth factor-receptor complexes initiate?
signaling cascades and cellular responses.
Pathogen Uptake
Pathogens like bacteria or viruses can enter host cells through endocytosis
What do some pathogens exploit?
receptor-mediated endocytosis mechanisms, enabling their entry into host cells.
Examples of mechanical signals
membrane tension, shear stress, Filopodia and Lamellipodia, extracellular matrix interactions
Stretch-Activated Endocytosis
Mechanical stretching of the plasma membrane, caused by factors such as cell movement or external forces, can activate endocytosis.
What can mechanosensitive ion channels and other proteins can sense, and what does it trigger?
membrane tension. Triggers endocytosis to help regulate membrane surface area
Fluid-Phase Pinocytosis
Cells experiencing fluid shear stress, such as endothelial cells in blood vessels, can perform pinocytosis (cellular drinking) in response to the mechanical stimulus.
What does Fluid-Phase Pinocytosis help cells to do?
helps cells uptake nutrients or clear debris from the extracellular environment.
Filopodia and Lamellipodia Formation
During processes like phagocytosis and macropinocytosis, cells extend membrane protrusions called filopodia and lamellipodia, respectively.
What are filopodia and lamellipodia driven by, and what can they probe?
by actin polymerization and can probe the extracellular environment.
What happens if filopodia and lamellipodia encounter suitable ligands or mechanical cues?
endocytosis can be initiated.
Integrin Signaling
Integrins, cell adhesion receptors, can transmit mechanical signals from the extracellular matrix to the cell interior.
What can integrin clustering and activation induce, and what does that influence?
an induce endocytosis, influencing cell adhesion and migration.
Spontaneous endocytosis
the continuous internalization of small vesicles from the plasma membrane without the need for specific external chemical signals
What does spontaneous endocytosis help cells to do?
regulate their surface area, retrieve membrane components, and maintain cell membrane integrity.
When will spontaneous endocytosis occur?
when it Lowers the Free Energy of the system.
What cellular mechanisms does the initiation of spontaneous endocytosis involve?
1. Membrane Tension and Curvature
2. Lipid Composition
3. Actin Dynamics
4. Dynamin-Independent Endocytosis
Membrane tension
When the plasma membrane experiences decreased tension due to various factors such as cell movement or mechanical stress, it can trigger spontaneous endocytosis
What does lower membrane tension promote?
the formation of membrane invaginations and subsequent vesicle budding.
Membrane Curvature
can arise due to the insertion of proteins or lipids that induce bending of the membrane
What can curved membrane regions facilitate?
The formation of endocytic pits, which are the initial structures of vesicle formation.
Lipid Rafts
a type of lipid composition rich in cholesterol and sphingolipids that can create
microdomains in the plasma membrane that favor spontaneous endocytosis
What do lipid rafts serve as, and what do they promote?
serve as platforms for clustering membrane proteins, promoting the formation of endocytic vesicles.
Actin Polymerization
Actin filaments can push the plasma membrane inward, forming endocytic pits. an ATP-driven process where ATP is hydrolyzed to provide the energy for the assembly and disassembly of actin filaments.
What are actin dynamics regulated by?
by various proteins and signaling pathways,
Dynamin
a GTPase essential for vesicle fission. essential for pinching off vesicles from the plasma membrane.
What happens to vesicles after endocytosis?
vesicles are transported along the cytoskeleton to reach their destination
What facilitates vesicle transport?
Motor proteins, such as dynein and kinesin
What do motor proteins require?
TP hydrolysis to generate the mechanical force necessary for vesicle movement.
What does membrane fusion require?
energy
SNARE proteins
essential for membrane fusion, undergo conformational changes that are ATP-dependent.
What gives the nuclear envelope shape?
• Nuclear lamin (Meshwork of intermediate filaments (type A and B))
• Sun-Linc Complex
• Nuclear Pore Complex
Sun-Linc Complex
• Holds the double membrane together
• Connects cytoplasm to the nucleus
• Required for intracellular force transmission (Is utilized for mechanotransduction; translates physical forces (compression, tension, shear stress) into biochemical signals)
Dilated cardiomyopathy
Impaired pumping of the left ventricle. Loss of muscle control causes the space to become dilated and impairs blood flow.
Arrhythmogenic cardiomyopathy
Heart muscles fail to contract properly, resulting in arrhythmia.
Emery-Dreifuss Muscular Dystrophy (EDMD)
Muscle wasting, cardiac weakness, and joint stiffness resulting from improper muscle formation and function
How many genes have been linked to EDMD, and how many of those genes encode components of the SUN-LINC complex?
6 genes, 4 linked to SUN-LINC complex
What makes EDMD a degenerative disease?
it causes a gradual, progressive breakdown and loss of muscle function and structure over time.
Satellite Cells
Specialized progenitor cells in muscle tissue
What does mechanical stress cause?
chromatin remodeling via the LINC complex
What does chromatin remodeling expose?
MRF promoter accessibility and causes production of MRFs
Nucleocytoplasmic Transport
A Gated Transport between cytoplasm and nucleus