Cell BIO
NOTES:
There are higher concentrations of the following in the cell:
K+ , Mg+ , PO4+3 , O2
There are higher concentrations of the following outside the cells:
Na+ , Cl- , HCO-3 , O2
Almost all diseases happen because the body is thrown out of homeostasis
“Everything exists to maintain homeostasis”
Positive feedback loops are part of a larger negative feedback loop
Cells broken up into percentage are made up of the following:
70-85% Water
10-12% Proteins
2% lipids
1-6% carbohydrates
Glycogen is higher inside the cell instead of glucose to keep a gradient to be able to pull glucose into a cell.
Plasma Membrane:
Made up of phospholipids and proteins
Phosopholipids are made up of three parts
Hydrophilic head
Glycerol backbone
Lipophilic tail
Cholesterol aids in helping stiffening the membrane
The number of cholesterol in the membrane is temperature dependant
Membrane proteins have different purposes:
Cell adhesion
GPI anchors
Transmembrane movement of water soluble substances
Pores/chanels
Carriers
Pumps
These use ATP
Can be enzymes
Cell to Cell communication
Molecule recognition
Attachment to cytoskeleton
Glycocalyx:
Membrane proteins with carbohydrate modifications
Have different purposes:
Negatively charge to repel other negatively charged protiens
They can interact with other glycocalyx of other cells
Act as receptors (insulin)
Important to immune system
Cytoskeleton:
Provides structural support
Allows cells to maintain shape
Maintains Polarity
Organizes intracellular organelles
Helps with movement and cell migration
Helps with transport
Microtubules
Largest of the filaments
Think of them like a hollow straw
Made up of a- and b- tubulin dimers
Constant growth and dissolution
Polymerization starts at the centrioles in the microtubule organizing center (MTOC)
They are the ones that pull the chromosomes to the side during splitting
Found in cilia, mitotic spindles, flagella, and the centrioles “conveyor belt”
Cilia is found in lung cells and the ear
Flagella is found on sperm cells
9+2 structures
They are paths for motor proteins
Kinesin and Dynein
Microfilament
Smallest of all the filaments but strongest
Provides elastic support
They attach to the adherin junctions
Important in muscle contraction
Actin and myosin
Associated with thick filaments (myosin in muscles)
Treadmilling constant building and breaking down
They consist of a head and a tail ATP hydrolysis causes a pivoting head.
Intermediate Filament
Think of them as box spring
They are permanent stable structure
They connect cellular structures
They are made of two polypeptide dimers wrapped around each other in antiparallel fashion. (rope like structure)
Connect desmosomes and hemidesmosomes together
Use different bases to make themselves depending on the cell type
Kertin (Hair)
Lamins
Vimentin
GFAP
Neurofilaments
Desmin
Cytokeratins
Cell Polarity each part of the cell has different job
Microvilli not on all sides of the GI cells
Directional transport
Barrier integrity
Organization
Claudins and Occludins means Closed
Tight Junctions (Zona Occludens)
Water tight “quilting”
Formed from alternating seams of claudin and Occludin proteins
Barriers: Seal the cells together so ions can't go in between the cells
Gates: Can be selective and let certain things in.
Fences: Separated the top of the cell and bottom of the cells
Anchoring Junctions
Mechanically attach cells together. NEED cadherins to mediate these attachments.
Different types:
Adherens junctions
Connect F-actin filament to cadherin
Cadherins form stable cell to cell junctions that link to the cytoskeleton of the other cell
Think of them like a belt goes all the way around the cell
Influence cell shape and mobility
If they don't work in cancer cells that cancer can metastasize
Desmosomes
Think of them as “rivets” or “spot welds”
Connect the intermediate filament to cadherins
Communicate extracellular forces to multiple cells
Allows some movement and some water and ions to move in the space between cells
Desmosomal cadherins link adjoining cells to intermediate filaments
Hemidesmosomes
Think of them as “wall screws” or “wall anchors”
Transmembrane connectors (integrins) attach to the intermediate filaments to the ECM.
Gap Junctions
Dense array of pores
“Tunnels” allow exchange of ions, sugars, amino acids, small molecules.
Permeability depends on intracellular pH and Ca+
Heart has a ton of gap junctions to help iron flow so it can contract unisonly
“Communicating junktion”
Mitochondria
Power house of the cell
Enslaved bacteria (theory)
2 membranes
The folds of the inner membrane are called Cristae
2 distinct compartments
Intermembrane space
Matrix space
ATP production
Mitochondria genome codes for mitochondrial tRNA and some mitochondrial proteins
Jobs:
Energy metabolism (ATP synthesis)
Energy stored in the proton gradient drives ATP synthesis
Intracellular Ca2+ reservoir (important for cell signaling)
Important in apoptosis
Cytochrome C is usually in the inner membrane but when released it starts apoptosis so no necrotising cell that burst this prevents inflammation.
Nucleus
Holds the genome and has the machinery necessary to maintain, copy and transcribe DNA.
Nuclear membrane is a double membrane the outer one is continuous with the rough ER and the inner membrane is smooth and connected to the nuclear lamina (intermediate filiments)
Lamina are structural support and rebuild the nuclear envelope in divided cells
Nuclear pores (look like flowers)
Are used to let mRNA out and let hormones and proteins (need a specific sequence to get in, NLS Nuclear locator signal) in
Nuclear Chromatin
Complex of DNA and DNA binding proteins in the nucleus is chromatin
Euchromatin: actively coding spread out
Near nuclear interior
Heterochromatin: tightly packed NOT transcribing
Hetero men do nothing so Heterochromatin does nothing either and is not transcribed
Near the envelope and nucleolus
Chromosomes are only visible as a distinct structure during Mitosis and Meiosis
During Interphase chromosomes occupy territories of the nucleus
Nucleolus
Cells ribosomes production factory
Assemble ribosomes in there
Not really a body more of a designated area dedicated to code for rRNA
Proteins need to be brought in after ribosomes made in nucleus because NO proteins are synthesised in the nucleus only the ER and cytoplasm
Ribosomes:
Complex of two protein subunits and ribosomal RNA
Free floating or bought to ER
Endoplasmic Reticulum (ER)
Biggest organelles in the cell
Cells factories for secreted proteins and lipids
One network of membrane enclosed tubules and sacs (Cisternae) continuous membrane
10% of total cell volume
Extends from the nuclear envelope throughout cytoplasm
The orientation of transmembrane proteins is established in the ER and maintained as they travel along the secretory pathway.
Transmembrane proteins CANNOT flip sides
Proteins and lipids are packaged in vesicles and transported from the ER to the Golgi
Smooth:
Contains enzymes for lipid, steroid and glycogen metabolism
Detoxification
The liver has a lot of smooth ER
Calcium Reservoir
Important for muscle contractions
Rough:
Ribosomes
Role in synthesis of secreted and membrane proteins and protein folding and posttranslational modification
Folding of proteins in the ER with the help of Chaperones
Chaperones: ATP-Hydrolyzing enzyme refolds heat damaged proteins. Folds proteins into a tertiary structure which is not energetically favorable but biologically favorable
Initial glycosylation of proteins happens in the ER (important for finishing of posttranslational modification in the golgi apparatus)
Manose is important in post translational modification
Add GPI anchors here for anchoring proteins of the cell membrane
Free floating ribosome proteins go to
Nucleus
Mitochondria
Peroxisomes
Bond ribosomal proteins go to:
Nuclear membrane
Golgi
Plasma membrane
Secretory vesicle
Endosomes
Lysosomes
Peroxisome membrane
Golgi Apparatus
The “finishing shop” for proteins and lipids
Made up of: cis-Golgi (close to the RER), medial-Golgi, trans-Golgi, and trans-Golgi network (the end facing the plasma membrane)
Job
Protien maturation
TARGET PROTEINS TO THEIR APPROPRIATE SUBCELLULAR LOCATION.
Recycling proteins
Synthesis of glycolipids and sphingomyelin (important in myelin sheath of neurons)
Type of modifications done in the Golgi determine the final destination after release from the golgi
Proteins destined for LYSOSOMES are modified by MANNOSE phosphorylation
In polarized cells proteins are sorted into distinct transport vesicles to reach specific plasma membrane domains
Lysosomes
Digestive organelles of a cell
Acidic so low pH
Acid hydrolases inside to help breakdown cellular debris and ingest materials
Proton pump makes the interior extremely acidic to help protein breakdown
Autophagy: self eating (done to old or damaged cell structures) MAINTAINS CELLULAR HOMEOSTASIS
Heterophage: degrading foreign material
LYSOSOME FORMS FROM THE TRANS-GOLGI NETWORK
ENDOSOMES BECOMES PHAGOSOMES
Peroxisomes
Peroxisomes because they have a lot of Peroxide in it
Oxidases: produces hydrogen peroxide
Catalase: neutralizes the hydrogen peroxide
Job
Lipid Metabolism
Myelin sheath of nerve cells
Oxidative reactions and detoxification
Breaks down various substrates
Metabolism of reactive oxygen species (ROS)
Reducing oxidative stress
Proteasome
Think of it as a paper shredder
ATP dependant
Recycles proteins marked with POLYUBIQUITIN CHAINS
Regulatory proteins that need to be inactive
Misfolded proteins
Non functional proteins
Viral proteins
Endocytosis: Comes into the cell
Extocytosis: Leaves the cell
Pinocytosis: drinking
Transcytosis: goes completely through the cell from one side to the other
Phagocytosis: eating
Extracellular Matrix
Fills space between cells and connects tissues together
Produced by cells in the ECM
Composed of secreted proteins and polysaccharides but varies by tissue type
Job
Structural and mechanical support
Pathways for cell regulation
Important in embryonic development
Provides survival signals and sequesters growth factors
Vital for tissue pathology and repair
Key components:
Matrix structural proteins (Collagen and Elastin) MACROMOLECULES
Matrix Polysaccharides (Glucosaminoglycans (GAGs), protoglycans) MACROMOLECULES
GAGs
Ground substance surround collagen and glycoproteins
Resists compressive forces on the matrix
Permits rapid diffusion of nutrients between blood and tissue cells
Bond ALOT of water (jello in Joints)
Mediates growth factor signaling
Also modulates cell signaling in general
Example: Hyaluronic Acid (Hyaluronan) LEGEND HAT which are used for intrajoint injections to help joint issues by increasing ground substance; it can be used on all animal types because no protein components so no immune response.
Proteoglycans
Bottle brush structure
Protein core (in cartilage)
HUGE molecules
Form aggregates with other GAGs matrix proteins
Core protein 5% mass and Pollysaccharide chain 95% mass
Adhesion proteins/glycoproteins (Fibronectin, laminin)
Cell Matrix interaction proteins (Integrins)
Collagen
MAJOR PROTEIN IN ECM
Resist tensile forces
3 alpha chains braided together so depending on the strands braided there is a lot of variability
RICH in glycine, proline, and hydroxyproline
Provides structural framework for ECM
Proline and lysine need to be hydroxylated in ER before use because it ensures proper folding of the helices
Vitamin C dependant process (scurvy)
Lysyl-oxidase enzyme crosslinks hydroxylysine for tensile strength
Without crosslinks you don't have a strong fiber
Collagen types:
Fibrillar
High tensile strength
Plywood like arrangement of the fibers
Found in loose connective tissues, tendons, bones, and cornea
Sheet-forming
Form nets that surround organs
Basal lamina beneath epithelia and muscles and nerve cells made of TYPE 4 COLLAGENS
Descemet membrane found in the cornea and needs to be see through so hexagonal pattern
Anchoring/Linking
Connect linear collagen fibers to other ECM components
Basement membrane
Elastin
Second most important after collagen
Tissue elasticity
5x more extensible then a rubber band
50% of the dry weight of the Aorta
Rich in proline so it can twist up
Fibrillin microfibrils scaffold with deposited crosslinked elastin
Adhesion Proteins
Link matrix components together and then to cells
Fibonectin and laminin make it up
Fibronectins are relatively small compared to collagen and elastin which are huge molecules
Fibronectin binds to integrins which are bound to the intracellular actin of the cytoskeleton so that's how they connect to the cells
Fibronectin is important in wound healing and cell migration
Laminin is essential for basal lamina
Integrins
TRANSMEMBRANE receptors connect to ECM with the cytoskeleton
Integrins attach cells to the ECM and link them to the cytoskeleton
Integrin function at:
Hemidesmosomes: provides stable adhesion and resistance to mechanical stress. Connected to intermediate filaments
Focal adhesion points: ECM dependant signaling to cells as well as cell migration, connect to Factin
Basal lamina
Basement membrane
Structural support
Major components are laminin (primary organizer of the sheet structure, three polypeptide chains alpha beta and y in crosslinked structure) and type 4 collagen (flexible and give the basal lamina tensile strength)
Integrins attach to lamin which attach to type 4 collagen which make fish net pattern.
Resident cells:
Fibroblasts: make most collagen, elastic fibers, and proteoglycans
Chondrocytes: secretes cartilage matrix
Osteoblasts: Produce calcified bone matrix
White and Brown fat cells
Transient cells:
Cells that move through the cell matrix but do not originate there example white blood cells
Both transient and resident cells need to be able to degrade the ECM for growth and movement. Resident cells also make ECM.
Matrix metalloproteases (MMPs) degrades the ECM
Tissue inhibitors of MMPs or TIMPs stop the MMPs (resident cells secrete these)
LEARNING OBJECTIVES:
1. List the principal membrane-bound organelles in an animal cell and state their primary functions.
Plasma membrane: To act as a selective permeable barrier that separates the cells internal environment from the outside. While regulating the movement of substance in and out.
Cytoskeleton: To provide structural support, shape, and internal organization while enabling cell movement and material transport.
Tight Junctions: To create a water tight semipermeable seal between adjacent cells that blocks movement of fluids, ions, and molecules through the space between them.
Anchoring junctions (Adherin junctions, desmosomes, and semidesmosomes): To securely connect neighboring cells to one another or to the extracellular matrix, providing mechanical strength and structural integrity to tissues.
Gap Junctions: To provide a direct channel for communication between neighboring cells by allowing the movement of ions, water, and small molecules.
Nucleus: Storage of genetic material DNA and managing all cellular activity
Nucleolus: Produce and assemble ribosomes
Ribosomes: Synthesize proteins by translating instructions from mRNA
RER: Protein synthesis , folding and modifications of proteins destined for cell membrane, secretion, or use within specialized organelles.
SER: Synthesis of lipids and phospholipids and steroid hormones.
Golgi Apparatus: To modify and sort and package proteins and lipids received from the ER so they can be used inside the cell or sent outside of it.
Lysosomes: To act as the cell's garbage disposal and recycling center by breaking down waster old cell parts and foreign invaders.
Peroxisomes: Lipid metabolism and detoxification of harmful substances through oxidation reactions (peroxide)
Proteasome: to degrade unneeded, damaged, or misfolded proteins by breaking their peptide bonds
Mitochondria: Power house of the cell ATP synthesis as well as Ca2+ storage and helps in apoptosis.
2. Explain how microtubules, microfilaments, and intermediate filaments differ in structure and how each supports cell shape, transport, and mechanical strength.
3. Describe and differentiate between tight junctions, adherens junctions, desmosomes, hemidesmosomes, and gap junctions in terms of molecular composition and physiological role.
4. Assess how combined defects in cytoskeletal networks and junctional complexes could impair epithelial integrity and contribute to clinical signs in animals.
5. Construct a labeled schematic of a eukaryotic cell showing organelles, cytoskeletal filaments, and junctional complexes, accurately depicting their spatial relationships and interactions.
6. List the structural components of a mitochondrion and name three of its key functions.
7. Explain how the chemiosmotic gradient across the inner mitochondrial membrane drives ATP synthesis.
8. Differentiate euchromatin from heterochromatin in terms of DNA packing, transcriptional activity, and nuclear architecture, and explain the role of lamins, nuclear pores and the nucleolus in genome regulation.
9. Describe the role of rER in translation and organelle targeting of proteins. Explain which proteins require translation in the rER, and describe ER dependent posttranslational modification.
10. Explain the special role of mannosidase in ER mediated protein synthesis.
11.Describe the structural organization of the Golgi apparatus and its role in protein and lipid processing, including glycosylation and vesicle trafficking.
12. Explain how proteins are targeted to lysosomes via mannose-6-phosphate tagging and the role of the trans-Golgi network in this process.
13. Differentiate between apical and basolateral protein targeting in polarized epithelial cells.
14. Summarize the functions of lysosomes in autophagy, heterophagy, and cellular homeostasis.
15. Identify the metabolic functions of peroxisomes, including lipid metabolism, ROS detoxification, and B-oxidation of very long chain fatty acids.
16. Discuss the role of proteasomes in ATP-dependent protein degradation, including the significance of polyubiquitin tagging and implications for cell cycle regulation and viral defense.
17. List major structural components of the extracellular matrix-including glycosaminoglycans, proteoglycans, collagen types, elastin, and adhesive glycoproteins-and describe their specific functions.
18. Describe how varying extracellular matrix compositions of different tissues varies (bone, cartilage, skin, basal lamina, and blood vessels) contribute to mechanical properties and physiological roles.
19. Describe the structure and functional importance of the basal lamina, including its key molecular components (e.g., laminin, collagen IV, etc.) and describe its biological function role in cell polarity and filtration.
20. Describe the role of matrix metalloproteases (MMPs), serine proteases and tissue Inhibitors of metalloproteases (TIMPs) for ECM remodeling. Why is remodeling important, and how does dysregulated degradation contribute to pathological conditions such as cancer, inflammation, and fibrosis?
WOOCLAP QUESTIONS:
1. Are sodium levels higher inside the cell or outside?
Outside
2. Tell me the size, what they're made of, and used for the different filaments.
Microtubules |
|
Microfiliment |
|
Intermediate Filament |
|
GAGs/Proteoglycans: Ground substance for matrix
Collagen: Structural framework of ECM
Elastin: Elasticity (especially in the lungs and blood vessels)
Adhesion Proteins: Adhesion and Communication
Type 4 collagen: important in the basal lamina