Chapter 2 - Cytology

Basic living, structural and functional unit of the body.
Models show "typical" cell.
Cells are atypical and diverse in form and function.

Cell Membrane (a.k.a. plasma membrane, plasmalemma)
Fluid in both structure and composition. Found at outer boundary of cell and delimits membranous organelles and their compartments.
Functions of Cell Membrane
1. Physical isolation
Provided by phospholipid bilayer.
2. Regulates exchange with environment
Serves as the "border crossing" for the cell.
3. Sensitivity
Has receptors for specific molecules.
Communicates with other cells.
Establishes an electrochemical gradient.
4. Structural support
Connected to the cytoskeleton of cell, other cells by linker proteins, and extracellular material.
Membrane Chemistry
About 50:50 proteins to lipids by weight. Dynamic structure characterized by fluid-mosaic model.
1. Phospholipids
Forms a phospholipid bilayer due to the hydrophilic and hydrophobic portions of the phospholipid molecules.
Prevents the passage of water and water soluble molecules.
Keeps extra- and intracellular compositions distinct and different.
2. Cholesterol
Helps to stabilize the membrane and maintain its fluidity.
1. Integral Proteins 
   Proteins embedded in the cell membrane that serve as:
a. Channels for water, ions and water soluble compounds.
b. Receptors
  c. Pumps transport ions or other molecules into or out of the cell.
d. Enzymes
2. Peripheral Proteins
   Attached to either the inner or outer surfaces of the cell membrane and serve as enzymes.
   Carbohydrate molecules attached to the outer surface of lipids (glycolipids) and protein (glycoproteins) molecules form the glycocalyx.
   The glycocalyx is involved in cell-to-cell communication, recognition and attachment.
Membrane Permeability 
Cell membrane is  selectively permeable.
Selectivity is based on size, electrical charge, shape, solubility or a combination of these factors.
The passage of molecules may be either:
Passive or not requiring the expenditure of energy.
Active or requiring the expenditure of energy.
A. Passive Processes Concepts in Biochemistry - Interactive Animations
1. Diffusion
   Net movement of molecules from a region of high concentration to a region of lower concentration.
2. Osmosis
   Diffusion of water from a region of high concentration to a region of lower concentration.
   Requires a membrane that prevents the diffusion of solute molecules.
3. Facilitated Diffusion
   Carrier proteins transport molecules that normally cannot cross membrane across the membrane.
   The transported molecules bind to receptor sites on the carrier proteins.
  B. Active Processes
       Active processes require energy usually in the form of ATP to transport substances against concentration gradients. There are three forms:
1. Active Transport 
   Requires energy in the form of ATP.
   Carrier proteins and enzymes must be present.
   Can move ions and molecules against concentration gradients (from a region of low concentration to a region of higher concentration).
   Examples are ion pumps that move ions such as sodium, potassium, calcium, magnesium against their concentration gradients.
   Exchange pumps exchange one ion for another, e.g. sodium/potassium pumps. Animation How the Sodium Potassium Pump Works
2. Endocytosis 
   Involves the engulfment of large volumes of material and formation of membrane bound spaces called vesicles.
   There are three types:
a. Pinocytosis (cell drinking) Animation of Pinocytosis
   Vesicles take in extracellular fluid. Nutrients within the fluid enter the cytoplasm by passive or active transport.
   These vesicles, pinosomes, can enter one side of the cell and expel their contents on the other as in cells lining blood vessels.
b. Phagocytosis (cell eating) Animation of Phagocytosis
   Cells take in solid objects (e.g. bacteria, cellular debris).
   Pseudopodia surround the object to form a vesicle called a phagosome.
   Vesicles then fuse with lysosomes which contain digestive enzymes.
   Phagocytosis is performed by specialized cells of the immune system.
c. Receptor-mediated endocytosis Receptor-mediated Endocytosis
   Vesicles form from regions of the cell membrane that contain specific receptor molecules.
   The receptors bind with specific target molecules called ligands.
   Examples of ligands include cholesterol and iron bound to their transport proteins in the blood.
3. Exocytosis Exocytosis Animation
   The reverse of endocytosis.
   Vesicles within the cell fuse with the cell membrane and release fluid and/or solids to the exterior.
Includes all the material within the cell membrane except the nucleus with its contents.Your text includes the nucleus in the cytoplasm but this is not the accepted definition in most texts.
There are two subdivisions of the cytoplasm, the cytosol and organelles.
A. Cytosol
Intracellular fluid that contains a high concentration of potassium and a low concentration of sodium. There is also an imbalance in the ions (charged molecules) inside and outside the cell so that the cytosol is usually negatively charged compared to the extracellular fluid.
Cytosol has a high concentration of dissolved and suspended proteins that give the cytosol a thicker consistency. (The term cytoplasmic matrix is now favored over cytosol because of the organized structure the high concentration of different-size molecules gives to this substance.)
Cytosol has small quantities of carbohydrates and large reserves of amino acids and lipids.
   Insoluble materials are sometimes present in the cytosol as inclusions.
   Examples of inclusions include glycogen, lipids and melanin.
B. Organelles
   These are distinct intracellular structures performing specific functions. There are two broad categories:
   1. Nonmembranous Organelles
a. Cytoskeleton
   Protein framework or interior scaffolding of the cell.
   Gives strength, flexibility and movement to the cell.
   There are four types of filaments:
1. Microfilaments
   Composed of a protein called actin.
   Anchors the cytoskeleton to integral proteins of the cell membrane, stabilizing the position of membrane proteins and mechanically strengthening the cell.
   Interacts with other filaments including myosin filaments to produce movement.
2. Intermediate filaments
   Intermediate in size.
   Intermediate filaments provide strength, stabilize organelles and transport materials
   For example, the shape of nerve processes are maintained by neurofilaments.
3. Thick Filaments
   These are composed of a protein called myosin.
   Thick filaments are abundant in muscles where they interact with thin filaments to produce contractions.
4. Microtubules
   These are composed of a protein called tubulin.
   Microtubules are the primary component of the cytoskeleton that give strength and rigidity to the cell.
   Assembly and disassembly of microtubules enable the cell to change shape.
   Microtubules attach to other organelles and move them around the cell.
   Microtubules form the spindle apparatus.
   Microtubules are formed and organized by the centrosome (a.k.a. microtubule organizing center).
   Microtubules are the structural component of centrioles, cilia and flagella.
b. Microvilli
   Finger-shaped projections of the cell membrane that increase surface area for absorption.
   Found on the cells of the small intestines and kidneys.
c. Centrioles 
   Cylinders composed of nine groups of microtubules arranged in triplets called a 9 + 0 array.
   Two centrioles are arranged at right angles to one another.
   The region of the cell containing these centrioles and the surrounding material is called the centrosome.
   Centrosomes form the spindle apparatus that directs the movement of the chromosomes during cell division.
   Centrosomes also form the basal bodies that migrate to the cell membrane and form cilia and flagella.
d. Cilia
   Cilia have nine groups of microtubules arranged in doublets that surround a central pair of microtubules.
   This array of microtubules is called a 9 + 2 array.
   Anchored to a compact basal body beneath the cell surface.
   Cilia beat rhythmically to move fluids or secretions across the cell surface.
   Cilia line the cells of the upper respiratory tract and oviducts.
e. Flagella
   Flagella are similar to cilia in structure except they are longer.
   Found only in sperm cells.
f. Ribosomes
   Ribosomes consist of RNA (60%) and protein (40%). There are about 80 different ribosomal proteins!
   Factories for the synthesis of protein.
   There are two kinds of ribosomes:
a. Free Ribosomes
   Scattered in the cytoplasm and produce proteins that enter the cytosol.
b. Fixed Ribosomes
   Attached to endoplasmic reticulum. Protein is produced for export from the cell or incorporation into membranes.
   2. Membranous Organelles
   All of these are delimited by a phospholipid bilayer membrane similar to the cell membrane.
a. Mitochondria (singular: mitochondrion)
   Mitochondria have a double membrane. The inner membrane has folds called cristae.
   The fluid within the inner membrane is called the matrix.
   Mitochondria produce ATP by breaking down organic molecules. Produces 95% of the energy needed by the cell to remain alive.
   This organelle consumes oxygen and produces carbon dioxide.
   Mitochondria have their own DNA and control their own growth and reproduction.
   Cells such as liver and skeletal muscle cells that demand a large amount of energy have many mitochondria.
b. Nucleus (kernel) (Again, not classified as a membranous organelle in most texts.)
   Nucleus determines the structural and functional characteristics of the cell by controlling what proteins are synthesized.
   Bounded by a nuclear envelope with a double membrane that separates nucleoplasm from cytoplasm.
   The double membrane encloses a perinuclear space that is continuous with the lumen of the endoplasmic reticulum.
   The nucleus communicates with the cytosol through nuclear pores.
   Fluid content of the nucleus is called nucleoplasm.
   The nucleus contains 23 pairs of chromosomes which are strands of DNA bound to proteins called histones.
   Loosely coiled chromosomes are called chromatin.
   Dense bodies within the nucleus called nucleoli (sing. - nucleolus) synthesize the components of ribosomes.
   Nucleoli are prominent in the nuclei of cells that produce a large quantity of proteins.
c. Endoplasmic Reticulum (ER)
   Organelle that consists of a network of intracellular membranes.
   Membranes form interconnected tubes, flattened sheets and round chambers all enclosing a fluid-filled space.
   The fluid-filled spaces are called cisternae (sing. cisterna)
1. Synthesis
   The membranes contain enzymes that synthesize carbohydrates and lipids and proteins when ribosomes are present on the surface.
2. Storage
   Synthesized molecules and molecules derived from cytosol can be stored in cisternae.
  3. Transport
   Molecules can move from one place in the cell to another by traveling through the cisternae of the ER.
4. Detoxification
   Cellular toxins are absorbed and neutralized by enzymes in membrane.
   Types of ER:
1. Rough Endoplasmic Reticulum (RER)
   Outer membrane surface is studded with ribosomes.
   Proteins and glycoproteins are synthesized and stored in the cisternae.
   Most of the proteins and glycoproteins are transported to the Golgi apparatus by transport vesicles.
2. Smooth Endoplasmic Reticulum (SER)
   SER synthesizes lipids and carbohydrates.
   Stores calcium ions.
   Removes and inactivates toxins.
 d. Golgi Apparatus (a.k.a. Golgi Complex)
   Organelle formed by a stack of flattened membranous discs called cisternae. (singular: cisterna)
   Most often the Golgi apparatus lies near the nucleus.  
1. Synthesis and packaging of secretions.
2. Packaging of enzymes for use in cytosol.
3. Renewal or modification of cell membrane.
   Vesicle Transport and Secretion
     Proteins and glycoproteins are synthesized in RER and transferred to the convex or forming face (a.k.a. cis face) of Golgi apparatus by transport vesicles.
     Enzymes modify the products as the product moves from one cisterna to the next by means of transfer vesicles.
     Product finally reaches maturing face (a.k.a. trans face) of Golgi apparatus and are discharged as secretory vesicles.
   Membrane Turnover
     When vesicles formed by the Golgi apparatus fuse with the cell membrane the membrane is renewed.
     This counterbalances the membrane lost by endocytosis.
e. Lysosomes
   Lysosomes are produced by the Golgi apparatus.
   Consist of vesicles containing digestive enzymes.
1. Breakdown and recycle old or damaged organelles.
2. Breakdown of materials brought in by endocytosis.
3. Breakdown of the cell itself (autolysis).
f. Peroxisomes
   Vesicles smaller than lysosomes and with oxidative enzymes that produce hydrogen peroxide.
   Peroxisomes may originate from RER.
   Contains catalase that breaks down hydrogen peroxide into water and oxygen.
   Peroxisomes absorb and neutralize toxins (e.g. phenols and alcohol)
Intercellular Attachment
   Intercellular attachment is achieved by cell adhesion molecules (CAMs) that are transmembrane proteins that attach to one another and to extracellular material.
   There are three kinds of cell junctions:
1. Tight Junctions
   Cell membranes are tightly bound by interlocking membrane proteins.
   Can block the passage of water and solutes between cells.
2. Communicating Junctions (a.k.a. gap junctions)
   Cell membranes are held together by membrane proteins called connexons.
   The connexons form channels between cells that allow small molecules and ions to readily pass from one cell to another.
3. Anchoring Junctions (e.g. desmosomes and hemidesmosomes)
   Cell membranes are held together by CAMs and proteoglycans.
   Anchoring junctions are attached to the cell's cytoskeleton and are very strong.
   They anchor and stabilize cells and help them to resist stretching and twisting.
Cell Life Cycle
   During interphase the cell is performing its normal functions and may be preparing for division.
   An interphase cell not preparing for mitosis (division) is in a G0 phase. Some highly specialized cells such as muscle cells and nerve cells remain in the G0 phase indefinitely.
   An interphase cell preparing for mitosis goes through the following phases:
G1 phase
   Cell produces enough organelles to make two functional cells.
   Cells may be performing their normal functions while in this stage.
S phase
   Follows the G1 phase and is when the chromosomes are replicated.
   Chromosome replication involves DNA and histone synthesis.
G2 phase
   This phase occurs before division begins and is a time for last-minute protein synthesis.
   Mitosis occurs in four stages but there is no precise boundaries between the stages.
1. Prophase
   Replicated chromosomes become visible as a pair of chromatids connected at a single point called a centromere.
   The centrioles move apart while producing microtubules that form the spindle apparatus.
   The nuclear envelope disintegrates and chromosomal microtubules of the spindle apparatus attach to a protein complex called the kinetochore that is associated with each chromatid.
   Other microtubules radiate from the centrioles forming astral rays.
2. Metaphase
   The microtubules push and pull the chromatid pairs until they are positioned in a narrow central zone called the metaphase plate.
3. Anaphase
   The chromatid pairs separate and the daughter chromosomes move toward opposite pairs of centrioles at either end of the dividing cell.
4. Telophase
   The nuclear envelope reforms and the chromosomes uncoil. Gradually, the chromosomes become no longer visible as distinct structures and nucleoli reappear.
   Cytokinesis is the actual separation of the cytoplasm of the two daughter cells.
   Cytokinesis begins in late anaphase as the cytoplasm around the metaphase plate constricts.
   The constriction gets deeper until two cells are "pinched" apart.