Notes on Basic Cell Physiology
Rahul's Noteblog
Notes on Histology
Notes on Basic Cell Physiology
Cytoplasm:
• Volume of the cell minus the nucleus. 70% water, 15-20% protein by weight.
Cytosol:
• Portion of the cytoplasm not contained in organelles. 55% of the cell volume.
Cytoplasmic Inclusions:
• Generally non-membrane bound chemical structures in the cytosol that may be stored energy sources or by-products of metabolism.
Organelles:
• Membrane limited cellular structures specialized for specific functions involving the synthetic and metabolic activities of the cell that require energy.
Plasmalemma (plasma membrane):
1. Boundary layer that maintains cytoplasmic integrity.
2. Regulates traffic of ions and molecules in and out.
3. Possess devices for attachment to other cells.
4. Possess devices for cell-cell communication.
5. Possess antigenic molecules which are the basis for cell recognition and tissue specificity.
6. Possess receptors.
Singer-Nicolson Model, 1972:
• Simplistically "protein icebergs floating in a sea of lipid."
1. Phospholipid bilayer is fluid.
2. Fluidity is dependent on lipid composition, cholesterol content and temperature.
3. Integral or intrinsic proteins may extend from one side of the membrane to the other.
4. Peripheral or extrinsic proteins generally held by weak electrostatic forces to one side of the membrane.
5. About 7 nm thick exclusive of cell coat.
6. Inner and outer leaflets have different lipid compositions.
7. Cytoskeletal interactions affect organization and mobility of surface membrane proteins.
8. Cell coat is made up of oligosaccharides bound to proteins in the outer leaflet.
Microvolli:
Microvilli on the surface of an egg Increase or decrease in response to activity of the cell or the environment Specializations of the free surface of the plasmalemma.
Regular array of microvilli in the intestine is termed a "brush border" due to it's regular array, much like Bart Simpson hair. These are stable structures with a core of actin.
Microplicae:
• Labyrinthine pattern of whorled ridges to hold surface mucous.
Pseudopodia:
• Meboid motility.
Stereocilia:
• Are very long microvilli in the epididymis.
Lamellipodia and Microspikes:
Lamellipodia: undulating membranes, palm of the hand.
Microspikes: fingers.
Exist in a migrating cell in tissue culture.
Cell Coat:
Cell coat is the surface layer of branching oligosaccharides of integral membrane proteins. The coat is particularly apparent on the apical surface of microvilli of the intestine where it is termed the glycocalyx.
Glycocalyx appears as a branching system of filaments emanating from MV. The appearance of the glycocalyx is made more apparent after staining with Alcian blue or ruthenium red.
Cell coat is the surface layer of branching oligosaccharides of integral membrane proteins. The coat is particularly apparent on the apical surface of microvilli of the intestine where it is termed the glycocalyx.
Physiology of the Cytoskeleton:
The cytoskeleton of eukaryotic cells is a system of 3 types of fibrous elements (microtubules, microfilaments, intermediate filaments) and accessory proteins associated with these elements. Together they spatially organize and restrict certain cellular functions via protein complexes and organelles and provide communication and motility paths between them.
Components of the cytoskeleton: Microfilaments (microfilaments) (actin) 6-8 nm Microtubules (microtubules) (tubulin) 25nm Intermediate filaments (IF) 10-11 nm.
Cytoskeletal proteins generally exist as a pool of monomeric subunits synthesized on free polysomes that can polymerize into helical, fibrous elements and depolymerize back to subunits for reuse. Hence, they provide a dynamic structural and contractile network. Tubulin microtubules and their accessory linker (MAPs and tau) and motor proteins (kinesin and dyenin) generally provide dymanic structural organization and motor potential.
Microfilaments:
Microfilaments are composed of actin and in concert with a variety of actin binding proteins (ABP) and other molecules like myosin, provides for motility, as well as maintaining tonicity and polarity of the cell via the cortical actin web. Intermediate filaments and their associated proteins (IFAP) are the most stable cytoskeletal polymers and provide a relatively permanent structural framework to terminally differentiated cells.
Microtubules:
Microtubules (microtubules) 25 nm hollow tube length variable 13 protofilaments when viewed in cross section unassembled heterodimer of alpha and beta tubulin gamma tubulin does not polymerize into microtubules but serves as a nucleus for polymerization.
Each heterodimer binds 2 molecules of GTP. One site on alpha tubulin binds GTP irreversibly and does not hydrolyze it. The 2nd site on beta tubulin binds GTP reversibly and hydrolyzes it to GDP and is called the exchangeable site.
Microtubule Organizing Centers:
Microtubules emanate from distinct and structurally diverse regions of the cytoplasm that adjust the local environment to favor nucleation and assembly of microtubules. These foci are termed microtubule organizing centers (microtubules OC).
Centrosome also termed the cell center. Other structures can serve as microtubules OC: basal bodies centrioles spindle pole bodies of fungi anastral spindle of plants.
Pericentiolar material or centrosome matrix contains gamma tubulin and pericentrin which interacts with alpha and beta tubulin to nucleate assembly.
Microtubules have polarity. Generally the minus end is nearest to the microtubules OC and the plus end is distal. There are exceptions: no obvious microtubules OC in dendrites and microtubules can have either + or - end near the cell body. All axons have the same polarity.
Microtubule Dynamics:
Conditions that favor assembly:
• Sufficient tubulin concentration.
• 37 C.
• Absence of calcium.
• GTP Plus end is the fast growing end also called the A or assembly end. Minus end or D for disassembly end grows slowly.
Dynamic instability model microtubules polymerize and depolymerize continually. While some are growing, some shrink.
During elongation GTP-containing tubulin adds to the microtubules ends. After the tubulin is incorporated, GTP bound to beta tubulin is hydrolyzed to GDP, therefore the end will have a GTP cap while the bulk of the microtubules will contain GDP. Microtubules have caps at both ends but there is more activity at the + end. When a microtubules grows rapidly, tubulin is added faster than GTP can be hydrolyzed, hence the cap. Because tubulin carrying GTP binds to another with higher affinity than tubulin with GDP, the GTP cap encourages microtubules growth. Once the GTP cap is lost, the microtubules will start to shrink.
Capped ends: Various capping proteins occur in the cytoplasm and may selectively bind to one or both ends of a microtubules and serve to stabilize it. microtubules OCs help to restrict the - end.
Anti-Microtubule Drugs:
Antimitotic drugs block assembly or disassembly. They fall into 3 classes: Depolymerizing drugs (colchicine, colcemid, nocadazole, podophylotoxin) depolymerive microtubules and consequently elevates levels of free tubulin. Stabilizing drugs (taxol) stabilizes microtubules and promotes tubulin polymerization. Sequestering drugs (vinblastine, vincristine) induce formation of large paracrystals of tubulin thereby removing them from the pool of available tubulin.
Microtubule associated proteins (MAPs) copurify with microtubules and induce microtubules polymerization by lowering the critical concentration for polymerization. They also modify the stability of microtubules and make them more resistant to depolymerization.
Microtubule-based Motile Systems:
There are three main examples of microtubules-based motile systems: movement of cilia and flagella movement of membrane bound organelles chromosome movements in mitosis microtubules motor proteins include: kinesin, a + end directed protein dyenin, a - end directed protein.
Cilia and Flagella:
Cilia are motile processes 5-10 micrometers long that project from the free surface of cells. Flagella are very long motile processes that generally propel whole cells. Both cilia and flagella have a core of microtubules called the axoneme.
Structure of the Axoneme:
The axoneme has a 9+2 arrangement of microtubules. 9 outer doublet microtubules are arranged in a ring with 2 single microtubules in the center. Outer doublet microtubules consist of an A subfiber with 13 protofilaments and a B subfiber with 10 protofilaments. The + ends are distal from the basal body. 2 dyenin arms project from the A subfiber and interact with adjacent B subfiber. Nexin joins adjacent outer doublets and radial spokes extend from each doublet inward.
Dyenin Cycles:
Regular cycles of conformational changes occur in dyenin powered by hydrolysis of ATP. This cycle moves the dyenin heads along adjacent microtubules causing sliding of microtubules toward the tip of the axoneme and the energy of sliding is translated into a bending movement. Nexin, radial spoke proteins keeps the axoneme together (in the fashion of a rubber band around a group of pencils).
Kartagener's syndrome (immotile cilia syndrome):
Hereditary defects in which cilia lack one or more components of the axoneme. Non-motile sperm and respiratory problems such as constant bronchitis and sinusitis are symptoms.
Membrane Transport in Microtubule Axons:
Membrane transport along microtubules in axons Axons lack protein biosynthetic machinery and all materials moved out axons from the cell body must be transported there by an active transport.
Fast anterograde axonal transport moves endoplasmic reticulum, etc. out the axon. The microtubules serve as railroad tracks and the motor force comes from kinesin. Kinesins exist at 2 groups: cytosolic kinesins involved in vesicle transport kinesin-related proteins (KRPs) involved in mitotic spindle assembly and chromosome movement.
There is evidence that membrane vesicles are carried by both microtubules and microfilaments. Both microtubules and microfilaments have been found bound to the same vesicle and cooperate in its transport.
Transport of synaptic vesicles in neurons is mediated by microtubules-kinesin, microtubules-dyenin through the axon but by microfilaments-myosin in the terminal cortex.
Additional Reading:
Basic Histology
1. Introduction to Histology
2. Basic Cell Physiology
3. Actin, Microtubules, and Intermediate Filaments
4. Mitochondria, Nucleus, Endoplasmic Reticulum, Golgi
5. Epithelium (Epithelial Tissue)
6. Connective and Adipose Tissue
7. Types of Cartilage
8. Osteogenesis
9. Nervous Tissue
10. Muscle Tissue
11. Cardiovascular System
12. Blood and Hematopoiesis
13. Lymphoid Tissue
14. Digestive Tract I: Oral Cavity
15. Digestive Tract II: Esophagus through Intestines
16. Liver, Pancreas, and Gall Bladder
17. Respiratory System
18. Integument
19. Urinary System
20. Endocrine System
21. Male Reproductive System
22. Female Reproductive System
23. Eye and Ear
Medical Images
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