CHAPTER 3  CELLULAR LEVEL OF ORGANIZATION

 

The cell is the basic structural and functional unit of all living things. Cytology is the study of cell structure. Cell physiology is the study of cellular function.

 

          DIAGRAM OF GENERAL CELL P. 61

 

A cell can be divided into 3 main parts:

 

I. Plasma (cell) membrane--outer limiting membrane separating the inside cellular contents from the outside surroundings

 

II. Cytoplasm—all cell contents inside the plasma membrane but outside the nucleus

      A. Cytosol—thick semifluid material containing water and various dissolved substances

      B. Organelles--highly organized structures with characteristic shapes--highly specialized for specific cellular activities

 

 [Cytoplasm is cytosol plus organelles and inclusions]

 

III. Nucleus—this is the largest organelle, but it is so important that it is given a special section of its own. It controls cell structure and most cell activities by the action of genes.

 

 

I. PLASMA MEMBRANE

Separates inside of the cell from the outside--gatekeeper that regulates passage of substances into and out of the cell.

   A. MEMBRANE STRUCTURE  (Review phospholipid molecules Ch. 2 p. 48 and see Fig. 3.2 p. 62)

 

The fluid mosaic model of membrane structure is the current description of the plasma membrane:

     Fluid—the plasma membrane resembles a sea of lipids. This layer holds together, but is is fluid and sloshes. Individual lipid molecules constantly move to different places within the membrane.

      Mosaic—scattered among the lipids are numerous protein molecules. Some float freely and some are attached at specific locations.  

        

      1. Lipid bilayer

         a. 75 % of membrane lipids are phospholipids. These molecules form the phospholipid bilayer (2 phospholipid molecules thick). They line up in a specific way in relation to each other, with the head portions of the molecules out and the tail portions in towards each other. The heads are polar and mix with water (hydrophilic). The tails are non-polar and do not mix with water (hydrophobic). A molecule with both of these characteristics is described as amphipathic.

         b. Other membrane lipids are cholesterol (which strengthens and stiffens the membrane) and glycolipids.

 

      2. Protein molecules are scattered among the lipids. They are of  2 types:

          a. Integral proteins--actually part of the membrane. Many integral proteins are transmembrane proteins--they extend through the bilayer and form tiny channels through which substances can flow (in or out). A few channels are open at all times but most have “gates” that can open and close under different conditions. The opening in the center of a channel protein is called a pore.

 

          b. Peripheral proteins--loosely attached to either the inside or the outside of the membrane. Could be removed without damaging the membrane.

 

 

Many membrane proteins are glycoproteins (protein + carbohydrate). The carbohydrate portion of these projects to the outside and forms a sugary coat around the cell called the glycocalyx. Functions:

           1. Recognition—allows cells to recognize each other

           2. Some cells use to stick together

           3. Protection of cells from enzymes in ECF

           4. Helps keep cells moist

 

 Functions of membrane proteins:

            1. Channels for moving substances in and out by diffusion through a water-filled pore

            2. Some are transporters. These can change shape to move a specific substance from one side of the membrane to the other.

            3. Some act as receptors which can identify and bind to a specific ligand which can be a hormone, a nutrient, etc. (A ligand is a molecule that fits into a channel or binds to a receptor by forces other than covalent bonds. )

             4. Enzymes---catalyze reactions inside or outside the cell

             5. Linkers---proteins that anchor filaments to the inside and outside of the cell. This provides structural stability and shape.

             6. Cell identity markers (antigens)--give blood type, for example, and allow us to recognize our own normal cells. Major histocompatibility (MHC) proteins are a very important class of cell identity marker. These are what is matched for transplants.

             

   B. FUNCTION OF THE PLASMA MEMBRANE

 

The plasma membrane acts as a barrier and a gateway at the same time. It encloses cellular contents and separates them from the extracellular fluid. The plasma membrane regulates entrance and exit of materials, permitting passage of some substances but not of others. If a membrane allows free passage of a substance it is said to be permeable to that substance. If it does not allow a substance to cross, it is impermeable to that substance. If some things are allowed to cross and others not, the membrane is selectively permeable. Factors that help determine permeability:

 

      1. Lipid solubility--substances that dissolve in lipids pass easily

      2. Size--small molecules cross more easily

      3. Charge--phospholipid bilayer part of the membrane is impermeable to ions, but some ions cross through channels or with the aid of transport proteins. Cations cross more easily due to the negative potential across the membrane.

      4. Presence of channels and transporters, which are specific for certain molecules or ions

      5. Very large molecules are unable to pass through the membrane except by endocytosis & exocytosis

 

For life processes to occur, substances must move in and out of cells by crossing plasma membranes. Substances needed in the cell are brought to ECF surrounding the cell by the blood and then must cross the plasma membrane.

 

 

 

 

 

 

 

 

 

 

 

    C. GRADIENTS ACROSS THE MEMBRANE

 

Since it is selectively permeable, the plasma membrane can be said to maintain an electrochemical gradient between the inside and outside of the cell.  

 

      1. Chemical gradient--this means that the chemical composition of materials inside and outside the cell differ.  For example, if we consider ions:

 

 

 

 

 

 

 

      2. Electrical gradient--inside surface of the plasma membrane is more negative than outside surface so there is a charge difference called the membrane potential across the membrane--more on this when we get to muscle & nerve

 

 

 

 

 

 

 

 

 

 

          D.  WAYS SUBSTANCES CROSS THE PLASMA MEMBRANE

       1. PASSIVE PROCESSES--all share 2 major characteristics:

·         Transport materials without using energy

·         Can only move materials from an area of greater concentration (or pressure) to an area of lesser concentration ( or pressure)

    2. ACTIVE PROCESSES---2 major characteristics:

·         All require energy (from ATP)   

·         Can move materials from an area of lesser concentration to an area of greater concentration

 

 

Another way the processes can be classified is according to whether they require the assistance of a transporter protein.

     If a transporter protein is required the process is mediated transport.

     If a transporter protein is NOT required, the process is nonmediated transport.

 

 

   E. PASSIVE PROCESSES (KINETIC ENERGY TRANSPORT)

      1. SIMPLE DIFFUSION--within substances ions and molecules are constantly in motion due to kinetic energy. This motion causes particles to mix within a solution.

 

If a particular ion or molecule is present in a higher  concentration in one area and a lower concentration in another area the difference is called a concentration gradient. Particles diffuse from the area of higher concentration into the area of lower concentration until the 2 concentrations become equal.  

Two other ways of expressing the same thing as the underlined section:

    WITH the concentration gradient

    DOWN the concentration gradient

         a. Simple diffusion can occur without a membrane involved

    1) Food coloring in water

              2) Smoke in air

         b. Simple diffusion also occurs across a membrane IF the membrane is permeable to the substance

            1) Directly through the phospholipid bilayer (if the material crossing is lipid-soluble)          

                       Water            Fat-soluble vitamins (ADEK)

    Oxygen           Glycerol

    CO2                           Small alcohols

    Nitrogen          Ammonia

    Steroids          Urea

 

            2) Through protein channels, which mostly are specific for just one substance, and in many cases can open and close

                  Na+         Cl-

                  K+          HCO3-  (bicarbonate ions)       

                  Ca2+        Water

 

Many of these channels are gated—some part of the molecule can move to block the pore at times. Some gated channels open & close at random; others are regulated by chemical or electrical changes.

 

Channels that are always open are called leakage channels.

   

The speed at which the concentrations become equal depends on several factors:

   1) Steepness of concentration gradient---the greater the difference between the two areas, the faster the diffusion rate

   2) Temperature---the warmer the faster

   3) Size of diffusing substance---the smaller the faster

   4) Surface area---the larger the area of membrane available the faster

   5) Diffusion distance---the thinner the membrane the faster

 

      2. OSMOSIS--net movement of water through a selectively permeable membrane from an area of higher water concentration to an area of lower water concentration This occurs when the membrane is permeable to the solvent but not to the solute. Plasma membranes are almost all permeable to water. Water diffuses both through the bilayer and through water channels called aquaporins.

 

 

 

 

 

 

 

 

 

 

 

 

A solution containing solute particles that cannot cross the membrane exerts a force called the osmotic pressure. The higher the concentration of solute particles the greater the osmotic pressure. Think of osmotic pressure as the measure of the tendency of a solution to draw water into itself and hold it. If two solutions are separated by a membrane that is permeable to water but relatively impermeable to the solute, the solution with higher osmotic pressure will draw water away from the solution with lower osmotic pressure while the solutes stay put.  

 

Osmotic pressure of cytosol is normally the same as osmotic pressure of the extracellular fluid outside. This means that the cell volume remains relatively constant.

 

Tonicity is a measure of a solution’s ability to change the volume of cells by altering their water content. Our red blood cells (which are surrounded by extracellular fluid--the blood plasma) maintain normal cell volume and shape because the plasma is isotonic to the cells--the concentrations of water and impermeable solute molecules are the same on both sides.

 

RBC can be removed and placed in an isotonic solution prepared to contain 0.9% sodium chloride (normal saline). The RBC membrane is permeable to water and impermeable to NaCl, so if RBC are removed and placed in a normal saline (isotonic) solution they maintain their size and shape.

 

Isotonic---osmotic pressure the same on both sides of the RBC plasma membrane    

 

 

 

 

 

 

        

 

Hypotonic---osmotic pressure higher inside the RBC plasma membrane

 

 

 

 

 

 

 

 

Hypertonic---osmotic pressure higher outside

 

 

 

 

 

 

 

 

 

                                   Read Medical Uses paragraph p. 69

 

      3. FACILITATED DIFFUSION--certain substances cannot cross by simple diffusion but still need to enter cells. Some of these can cross by facilitated diffusion. The substance still must move with the concentration gradient but it is done with the help of certain integral protein molecules called transporters. These transporters are very specific and can only transport one certain substance, molecule by molecule.

            Steps for moving a substance in:

      1) One molecule of the substance attaches to the transporter on the outside of the membrane, forming a temporary combination called a complex

      2) This causes the shape of the transporter to change (see Fig. 3.10 p. 69)

      3) Since the open end of the transporter is now to the inside of the cell, the molecule  is released inside

      4) Transporter can then return and attach to another molecule and repeat the process

      5) Can continue until the concentrations become equal.

 

The substance being brought in will probably be used up in chemical reactions, which keeps the concentration inside the cell low.

 

Facilitated diffusion can be as fast or faster than simple diffusion. Things that move this way:

       Glucose       Ions                   Certain amino acids

       Galactose     Urea

       Fructose      Certain vitamins

 

Transport maximum---this is determined by the number of facilitated diffusion transporters present. Once all the transporters are working as fast as they can, further increases in the concentration of the substance being transported do not increase the rate of transport.

 

Glucose is transported into cells by facilitated diffusion. Insulin comes into the picture by causing cells to insert large numbers of transporter proteins for glucose into their plasma membranes. This increases the transport maximum for glucose to a level that meets the needs of the body. Some glucose can enter cells without insulin, but not enough.

       

 

  

 F. ACTIVE PROCESSES--ALL SHARE THESE CHARACTERISTICS:

·         All require energy from ATP

·         Can move AGAINST the concentration gradient

Active processes can transport substances that are too big, have the wrong charge, or need to move against the concentration gradient.

 

      1. ACTIVE TRANSPORT--moves various ions, amino acids and monosaccharides (some of these are also brought in by other methods). A protein transporter, often called a pump, is required.          

      a. PRIMARY ACTIVE TRANSPORT—energy from ATP is used to directly change the shape of the transporter protein. Steps:

        1) A molecule on one side of the cell binds with a transorter protein (highly specific to that substance and not the same ones that do facilitated diffusion)

        2) This binding causes an ATP molecule to split off its third phosphate group and attach the phosphate with its energy to the pump (transporter) protein

        3)  The energy is used to change the shape of the transporter so that the molecule is released on the other side of the plasma membrane

        4) Transporter protein returns to original shape and can repeat over and over

 

A very important active transport mechanism is the Na+/K+ pump.

 

 

 

 

 

 

 

 

Na and K constantly (slowly) leak the wrong way by simple diffusion. Also in some cells physiological processes interfere--so all cells have Na/K pumps that operate continuously. These can move thousands of molecules in a fraction of a second.

 

Other active transport mechanisms move Ca2+ ions, sugars and amino acids.

 

          b. SECONDARY ACTIVE TRANSPORT---ATP energy establishes an ionic concentration gradient that then drives substances across the membrane—found in certain areas such as the small intestine and kidney. By keeping the Na+ ion concentration high outside and very low inside cells, this allows Na+ combined with another kind of molecule such as glucose to be  drawn into cells. The pull for Na+ is so strong that it can even pull glucose in with it AGAINST the glucose concentration gradient.

 

Symporters—transport proteins that always must move 2 substances at once in the same direction—can only operate when both are present

 

Antiporters—one thing goes one way, another goes the other way (one in, one out)

 

      2. TRANSPORT IN VESICLES--moves larger substances such as bacteria, RBC and very large molecules. (What is a vesicle?? )

         a. ENDOCYTOSIS—3 types, all move things INTO cells

             1) PHAGOCYTOSIS--"cell eating" moves solid particles in. Extensions called pseudopods surround the particle and it is drawn into the cell. A phagocytic vesicle (phagosome) is formed and the particle is digested by enzymes. Only certain cells in the human body carry on this process—WBC.

            2) PINOCYTOSIS--"cell drinking" engulfs liquid droplets. No pseudopods but otherwise the same. A pinocytic vesicle  is formed. Most cells do this. Also called bulk-phase endocytosis.

             3) RECEPTOR-MEDIATED ENDOCYTOSIS--highly selective--cells bring in specific requirements--ligands in ECF bind to specific receptors and then are brought in by endocytosis. Steps and a helpful illustration are on page 73. Things commonly brought in this way:

                     Cholesterol             Hormones

                     Iron                        Some viruses—they are tricky & fool the cell into this

                     Vitamins

         b. EXOCYTOSIS--moves things OUT instead of in (still under the heading of  bulk transport)--often moves secretions that will serve their purpose outside cells, Secretory vesicles are formed, move to and fuse with the plasma membrane, releasing their contents to the ECF.

·         Nerve cells release neurotransmitter

·         Secretory cells release their secretion

 

         c. TRANSCYTOSIS—this is not exactly a separate process. It refers to taking in a substance by endocytosis on one side of the cell, moving it directly through the cytosol, and sending it out by exocytosis on the other side. The substance is not changed as it passes through.      

 

          SUMMARY OF ALL MEANS OF TRANSPORT  TABLE 3.1 PAGE 75

 

 

II. CYTOPLASM---all contents inside the plasma membrane but outside the nucleus

    A. CYTOSOL—semifluid gel-like material that is 75 - 90% water with:

           1. Dissolved substances:

                a. Inorganic molecules such as ions

                b. Smaller organic molecules (simple sugars, amino acids)

 

            2. Suspended substances such as :

                a. Larger organic molecules

                     1) Proteins including enzymes

                     2) Lipids

                     3) Glycogen

Suspended substances are in the form of a colloid—particles remain suspended in the medium although they are not dissolved—have like charges which repel each other.

 

3. Organic molecules may collect (aggregate) in masses for storage. These are

known as cellular inclusions and may appear and disappear as conditions change.

     a. Lipid (triglyceride droplets)---stored fat

     b. Glycogen granules---storage form of glucose

     c. Melanin---pigment

 

Many chemical reactions occur in the cytosol, esp. among the dissolved substances. Since enzymes catalyze most of our chemical reactions, cytosol contains large numbers of enzymes. This is the intracellular fluid we mentioned in Chapter 1.

 

    B. ORGANELLES--specialized structures with recognizable shapes that have specific functions within cells. The number and type of organelles within any cell depends on the function of the cell. Each organelle has its own job and carries out its own processes, but all cooperate to maintain homeostasis.

 

Some organelles are in direct contact with the cytosol:

      Cytoskeleton

      Centrosomes

      Cilia

      Flagella

      Ribosomes

 

Others, known as membranous or membrane-bound organelles, are surrounded by their own membranes and separated from the cytosol:

      Endoplasmic reticulum

      Golgi complex

      Mitochondria

      Lysosomes

      Peroxisomes

      Proteasomes

      Nucleus

 

 

      1. CYTOSKELETON--network of protein filaments in the cytosol

         a. Functions

              1) Structural framework

              2) Help organize cell contents

              3) Transport of chemicals

              4) Movement of whole cells

              5) Movement of organelles within a cell

         b. There are 3 kinds of filaments:

             1) Microfilaments—thinnest—made of protein actin and concentrated in the periphery of the cell. Functions:

                 a) Movement—muscle contraction in muscle cells, cell division, cell locomotion

                  b) Mechanical support, shape and strength of cells

                  c) Provide support for microvilli—these are projections of the plasma membrane that increase the surface area for absorption in certain cells

             2) Intermediate filaments—combination of several proteins--strong and tough. Structural reinforcement and hold organelles in place.

             3) Microtubules—thickest—made of the protein tubulin, these have a hollow center and radiate out from the centrosome toward the periphery of the cell.  Function in support and shape, transport of substances and organelles, assist in movement of chromosomes during division, movement of pseudopods, and movement of cilia and flagella.

 

      2. CENTROSOME---this organelle is located near the nucleus and has 2 components:

           a. Centrioles---within the pericentriolar area are a pair of  cylindrical structures called centrioles, which lie at right angles to each other. Each centriole is made up of 9 clusters of  3 microtubules each (triplets) arranged in a circular pattern. Centrioles are essential for cell division and play a role in formation of cilia and flagella. As a cell prepares to divide, cnetrioles will replicate.

            b. Pericentriolar material---region of cytosol which surrounds the centrioles. It contains hundreds of ring-shaped structures made of tubulin. It is an organizing center for the mitotic spindle and for microtubule formation.

 

      3. CILIA AND FLAGELLA---some body cells have projections for moving the entire cell or moving substances along the surface of the cell. Both of these projections, cilia and flagella,  contain cytosol and are covered by the plasma membrane of the cell they are a part of. They have an inner core of 20 microtubules.

         a.. Cilia---in the human body, cells with cilia remain still while the cilia sweep something past

·         Many---thousands cover cell surface

·         Short and hairlike

·         Anchored to a basal body just inside the plasma membrane

·         Wavelike motion

·         Respiratory tract, Fallopian tubes

 

         b. Flagella---movement of entire cell---swims through a liquid

·         Few or single

·         Relatively long

·         Whiplike motion

·         Sperm are our only example

 

      4. RIBOSOMES—the ribosomes are the organelles that carry on protein synthesis. They are tiny spheres made of ribosomal RNA and ribosomal proteins (mostly enzymes). rRNA and other components are synthesized in the nucleolus. Each ribosome consists of 2 subunits, one large and one small. The subunits are assembled in the nucleus and leave separately through nuclear pores to be assembled in the cytosol.

         a. Some, the free ribosomes, are loose in the cytosol and mainly synthesize proteins for use in the cytosol.

         b.  Others are attached to ER (membrane-bound ribosomes) and these synthesize proteins that will be used in the plasma membrane or exported from the cell.

         c. Mitochondria have special ribosomes of their own and use them to synthesize mitochondrial proteins

   

 

      5. ENDOPLASMIC RETICULUM (ER)—network of folded membranes that form flattened sacs or tubes. These are continuous with the nuclear envelope. 2 types:

         a. Rough ER--studded with ribosomes, has a rough or beaded appearance. The membrane forms flattened sacs that are continuous with each other, the nuclear envelope, and the smooth ER. Functions:

            1) Proteins made by attached ribosomes enter the ER sacs as they are assembled. There they will be processed and sorted

            2) Enzymes inside the ER may add carbohydrates to the protein molecules, forming glycoproteins.

            3) Phospholipids are synthesized and may be added to protein molecules by different enzymes

            4) Sections of phospholipids with proteins already built in may be sent to repair or replace area of various organelle membranes or the plasma membrane

             

         b. Smooth ER--no ribosomes associated, extends from rough ER. The membrane is more tubular. Functions:

             1) Synthesis of fatty acids

             2) Synthesis of other lipids, including steroids

             3) Associated enzymes change glycogen to glucose when needed for energy

             4) Other enzymes inactivate or detoxify various drugs and toxic materials

             5) Stores and releases Ca2+ ions in muscle

          

 

 

      6. GOLGI COMPLEX (APPARATUS, BODIES)--Located near the nucleus --usually one per cell, larger numbers in secretory cells. Consists of 3 - 20 flattened sacs called cisternae stacked on each other. Different cisternae contain different enzymes.

 

In general, the Golgi complex processes, sorts, packages and delivers proteins and lipids to the plasma membrane, lysosomes and secretory vesicles.

         a. Proteins arrive from rough ER in a transport vesicle and go into the entry (cis) face of the Golgi complex.

         b. Protein may be modified and then moved on to one or more medial cisternae by transfer vesicles

         c. After further modification, the protein is transported to the exit (trans) face, where still more modification may be done. The proteins are sorted and packaged. What happens next depends on the purpose of the protein.

            1) Some leave the exit face in secretory vesicles, which will deliver the protein to the plasma membrane and release it by exocytosis.

            2) Some leave in vesicles that will carry them to be incorporated into the plasma membrane

            3) Some leave in vesicles called storage vesicles and will remain in the cell (most of these are lysosomes). If an existing lysosome runs short of enzymes, the Golgi complex can package some up in a vesicle and send them to the lysosome.

         d. The Golgi complex also synthesizes certain carbohydrates.

 

 

    COMPLETE STORY OF PROTEINS MANUFACTURED FOR EXPORT:

 

           Ribosome

                 ?

           Rough ER

                 ?

           Transport vesicles--formed by a piece of rough ER membrane

                 ?     

           Golgi complex--enters outer cistern closest to nucleus, moves thru

                 ?

           Secretory vesicle

                 ?

           Exocytosis

 

      7. LYSOSOMES--membrane enclosed vesicles formed in the Golgi complex that contain powerful digestive enzymes. Functions:

      1. Enzymes digest bacteria and other substances that enter by endocytosis

      2. Break down chemical by-products produced by cellular metabolism

      3. Engulf and digest worn-out cell parts, recycling the chemicals--autophagy

      4. Destroy cells damaged beyond repair--autolysis

      5. All lysosome membranes break down after death & this accounts for some postmortem change

      6. Lysosome enzymes are released from sperm to aid in penetration of the egg

      7.  Lack of the ability to synthesize certain ones of the lysosome enzymes can cause inherited diseases such as Tay-Sachs disease.

 

All lysosome enzymes, which come in as many as 60 different kinds, can be called lysozymes or hydrolases as a group. They act best in an acid pH, so lysosome membranes pump H+ ions into the vesicle to enhance the activity of their enzymes.

 

      8. PEROXISOMES--similar in some ways to lysosomes but these contain different enzymes. Their enzymes are called protesases. Peroxisomes function in normal metabolism of fatty acids and amino acids. Their enzymes can detoxify certain harmful substances--esp. important in liver and kidney.

Peroxide is produced as the enzymes act. This would be harmful to the cell, so the peroxisomes also contain an enzyme called catalase which breaks down the peroxide before it ever enters the cytosol.

 

It is currently believed that existing peroxisomes self-replicate when new ones are needed.