Dr. Guglielmo introduction to cell phys Flashcards
What is cell physiology?
Study of how cells work together to perform functions in a living organism
State the similarities and differences of cells
Similarities:
-Contain DNA
-Cytoplasm - require energy
-Cells enclosed in plasma membrane
Differences:
-Variability of cell shape
-Organelle #
-Membrane protein composition
-Genome expresion
What is the Morula?
Stage of development when there are 32-64 cells (Mulberry in latin)
What are the two populations of cells you get during development?
- Outer cell mass trophoblasts = becomes placenta
- Inner cell mass embryoblasts = some become embryo
What are the two types of inner cell embryoblasts?
- Hypoblasts - connected to blastocyst cavity - attach to sides and become part of this
- Epiblasts become the embryo
What does the blastocyst cavity become?
The primitive yolk sack
Where does the blastocyst get planted?
In the uterine wall
Why does amniotic fluid wrap around the embryo?
Helps cells on top get nutrients
What is the significance of the primitive streak?
Cells on either side divide and migrate. Populate bottom first, then middle
What are the three germ layers, in order from top to bottom?
*Where do they come from?
Ectoderm
Mesoderm
Endoderm
Nutrients and oxygen available in embryo location dictate what kind of cells they become.
*These are established from the epiblast cells in the embryo.
What is the Ectoderm?
Exterior of the embryo, precursor to epidermis and the nervous system.
-Nervous system and epidermis (skin, hair and nails)
-Top layer
*Memory trick
- ecto = outside - outer of embryo
- attractoderm, can be attracted to someones looks and brains
What is the Endoderm?
Interior of the embryo, precursor to the gut and its appendages (alveolar cells, thyroid cells, pancreatic cells).
-Digestive tract, liver, pancreas, respiratory systems, and bladder
-Bottom layer
*Memory trick
- endo = internal, everything inside your body
What is the mesoderm?
Cells in between the two layers, precursor to muscle and connective tissue (red blood cells, tubule cells, cardiac muscle, skeletal muscle, and smooth muscle).
-Skeleton, muscle, circulatory and lymphatic systems, and gonads
-Middle layer
*Memory trick
- movederm = everything required to move
What are the different tissue types?
- Nervous tissue (brain, spinal chord - mental activity, sensory input and integration, regulates homeostasis, regulates muscles and glands)
- Muscular tissue (skeletal, cardiac, smooth muscle - contraction, movement and support)
- Connective tissue (2 branches, fat vs collagen based - provides energy storage and organ protection vs tendons and cartilage)
- Blood (red blood cells, platelets - regulate nutrient and oxygen transport, metabolic waste, immune system)
- Epithelial (lines surfaces and cavities - secretion, absorption, protection, etc)
What is the ECM?
Extracellular matrix
Meshwork of proteins and polysaccharides. Secreted by cells into the spaces that surround them (specialized cell make a lot of the ECM)
What does the ECM do?
-Holds cells and tissues together
-Organized environment for cells to move and interact
-Bidirectional transfer of information (outside - neurosn)
-Regulates proliferative capacity, differentiation and survival
Functions as: structural (bone + teeth), tensile strength (tendons), transparent matrix for sight (cornea), control cell behaviour (basal lamina @ interface between epithelium and connective tissue.
Describe epithelial cells
-In the epidermis
-Polarized: simple epithelium, apical surface faces lumen of a tube or external environment
-Spindle orientation and cell fate determination (knows which side is outside vs inside)
-Basal surface rests on and associates with the basal lamina
-Connected with adjacent cells by specialized attachments including tight junctions, desmosome and gap junctions.
*Minor role in producing matrix
What is the basal lamina?
ECM that supports epithelial cells
Describe fibroblasts
-In the dermis
-Not attached to adjacent cells (can move around)
-do not have apical-basolateral polarity (don’t have orientation)
-have leading edge and lagging end polarity (migration)
-are in contact with ECM (via focal adhesions) - cells sparsely distributed in the matrix
*Major role in producing matrix
What are hemidesmosomes?
Integrins (transmembrane proteins) bind to intermediate filaments - stable, don’t move
What are focal adhesions?
Integrins (transmembrane proteins) bound to Actin cytoskeleton - transient, can be released.
Found in all cells but usually those that migrate more
What are the 3 types of cell junctions?
Anchoring junctions (only one that can be both cell-matrix and cell-cell, other two just cell-cell), occluding junctions (block junctions - e.g. block water), and communicating junctions.
What is collagen?
*structure, where are they made
-Major component of the ECM - most abundant protein in mammals (1/3 of whole body protein content)
-28 types in human genome (family)
-3 polypeptides come together to form trimeric structure (3 amino acid motif that repeat in corkscrew mostly -alpha- always Glycine, then Proline and hydroxy proline+ hydroxylserine are common = GXY - can have other amino acids)
-Made by fibroblasts
-Form insoluble fibers
Describe the collagen biosynthesis steps
- Polypeptide synthesis
- Post-translational modifications (dependent on vitamin C)
- Multimer assembly - procollagen assembly (defect = osteogenesis imperfecta, brittle bone disease)
- Higher order assembly
- N-linked oligosaccharide modification
- Procollagen processing - C- and N-terminal propeptide cleavage (defect = Ehlers- Danlos)
- Fibrillogenesis (crosslinking)
- ECM superstructure formation.
What are the differences between collagen types?
-# of helix repeats (length of triple helix)
-shape of globular C + N domains
-Covalent modification differences to triple helix (e.g. other amino acids present than core 3)
Describe type I collagen
-structural feature
-representative tissue
-gene(s)
-structural feature: Fibrillar, heterotrimeric (more than one gene)
-representative tissue: skin, bone, ligaments
-gene(s): COL 1 A1, COL1 A2 (two proteins from one gene, one from the other, not set which)
Describe type II collagen
-structural feature
-representative tissue
-gene(s)
-structural feature: Fibrillar, homotrimeric (one gene)
-representative tissue: cartilage, vitreous humour
-gene(s): COL 2 A1
Describe type IV collagen
-structural feature
-representative tissue
-gene(s)
-structural feature: Sheet-forming, heterotrimeric
-representative tissue: basal lamina
-gene(s): COL 4 A1 - COL 4 A6 (6 genes)
Describe type VI collagen
-structural feature
-representative tissue
-gene(s)
-structural feature: Beaded microfilaments, heterotrimeric
-representative tissue: skeletal muscle
-gene(s): COL 6 A1, A2, A3, A5
Describe type VII collagen
-structural feature
-representative tissue
-gene(s)
-structural feature: Fibril-associated (anchoring), homotrimeric
-representative tissue: Dermis
-gene(s): COL 7 A1
Describe type XIII collagen
-structural feature
-representative tissue
-gene(s)
-structural feature: Transmembrane, homotrimeric
-representative tissue: hemidesmosomes in skin
-gene(s): COL 13 A1
What is Osteogenesis Imperfecta? What causes it?
“Brittle bone” disease (type I collagen).
Autosomal dominant genetic disorder (COL 1 A1, and A2 genes). Causes improper helix formation due to glycine substitution to other amino acids.
Impaired pro-collagen transport to Golgi apparatus, therefore low collagen - fibril failure during stress (bone has collagen fibrils that go through - allows bones to bend a little - less brittle, like rebar in concrete).
What are Glycoproteins?
Proteins that have sugar(s) attached to protein core
What are Proteoglycans?
Specialized repeating sugars mostly attached to a protein core: Glycosaminoglycans (GAGs).
-Bind cations and water, regulate the movement of molecules through the matrix, cushioning (e.g. Perlecan in basal lamina and Aggrecan in joints - most common)
What are GAGs?
Glycosaminoglycans
Long, linear carbohydrate polymers
e.g. Chondroitin sulphate (cartilage), Keratan sulphate (cornea, cartilage and bone), Heparan sulphate (ubiquitously expressed, binds ligands involved in angiogenesis and tumor metastasis.
-Possible to mix GAG types in a structure - doesn’t have to be the same type throughout.
What are multi-adhesive proteins?
-Long flexible macromolecules -Like glue in the ECM
e.g. Laminin
-Bind to a variety of components (collagen, polysaccharides, cell surface receptors, growth factors, hormones, etc.)
-Major role is to attach cells to the extracellular matrix by cross-linking the matrix to the cell membrane e.g. Fibronectin
-Important in wound healing and cell migration. Functions to help cells attach to other ECM components.
Describe integrins
‘Bridge’ between ECM and the cytoskeleton. Adhesive receptors. Bind the matrix as heterodimers.
What is Epidermis Bullosa?
Group of inheritable disorders
Characterized by epidermal fragility with blistering and erosions - weakening between epidermis and dermis
Regardless of where mutation occurs phenotype is same
-several mutations/ diseases under umbrella EB
e.g. butterfly children - skin is delicate as butterfly wing (benign - playing w friends, severe - putting on clothes)
What are CAMs?
Cell adhesion molecules:
-integrins
-selectin
-ig-Superfamily
-Cadherin
What are selectins?
-Divalent cation dependent (Mg2+, Ca2+) opens up binding site, removed & binding sites will close- e.g. starved cells detach
-Heterophilic binding
-Carbohydrate binding: E-selectin (endothelial), L-selectin (leukocyte), P-selectin (platelet)
-Play an important role in host defense mechanisms
Describe the Ig Superfamily
Calcium independent
Characteristic immunoglobulin domains
Homophilic: 2 identical Ig CAMs binding to each other e.g. two NCAMs (neural)
Heterophilic: e.g. binding of Ig family member ICAM (intercellular) to lymphocyte function associated antigen-1 (LFA-1) s T-cell specific integrin
What are Cadherins?
Calcium dependent - Homophilic binding
Cadherins bunch together and then reach across and make a stronger bond with another bunch of cadherins
-Subclasses: P-cadherin (placental), N-cadherin (neural- also in mesenchymal cells), E-cadherin (epithelial)
What are properties that affect cell-cell adhesion strength?
-Binding affinity
-Spatial distribution (how many can you bunch up)
-Activity state of adhesion molecules (e.g. phosphorylated)
-External forces surrounding the cells (more stress on cell = larger chance of breaking bond)
What are anchoring junctions? Give examples
Mechanically attach cells to neighbouring cells or ECM
Cell-matrix: hemidesmosomes (integrins to intermediate filaments), focal adhesions (integrins to actin)
Cell-cell: adherens junctions (actin and cadherins), desmosomes (intermediate filaments and cadherins)
What are Occluding junctions?
Give examples of permissive and not permissive occluding junctions
Tight junctions - Prevent small molecule passage, commonly found in polarized epithelia
Protect self from non-self - “leakiness” altered due to tight junction changes allowing or not allowing for paracellular transport
Permissive: Claudin 2, and claudin 16
Not permissive: Claudin 8, and claudin 4
What is paracellular transport?
Transport between two cells
What are communicating junctions? What is the protein that makes up communicating junctions?
Gap junctions - Channels that mediate passage of ions/ solutes or electrical signals from one cell to its partner
- Connexin (protein that make up communicating junctions
-6 Connexins come together to make connexon, connexon A + B make a bridge from one to the other and dock to make junction
-Most fragile junction, can be broken easily
What is cardiac myocyte junction disease?
Arrythmogenic Right ventricular cardiomyopathy (ARVC)
-Anything affecting the gene creating desmosome + adherens causing issues to gap junctions
What is Carcinoma?
Cancer of skin or tissues that line internal organs
-Subtypes: adenocarcinoma, basal cell carcinoma, squamous cell carcinoma, etc.
