Snapshots of Science & Medicine
Activity 1,  Teacher’s Edition

Molecular Recognition and the Immune Response
Prepared by Fred Sculco, Morrison Chair in Science, Noble and Greenough School, Dedham, Mass.

Introduction
This activity gives students hands-on experience in three-dimensional model building. It’s designed to help students understand the importance of molecular shape and charge in molecular-recognition, and to understand the importance of molecular recognition to immune-system function. It also provides an excellent opportunity to review the structure of cell membranes.

Objectives

  • Understand the interaction between antigens and antibodies.
  • Understand how molecular shape and charge allow specific molecular interactions.
  • Design and build 3-D visual models to represent molecular-recognition events.
  • Diagram the structure of cell membranes.
  • Understand how scientists use molecular models to design therapeutic drugs.

Materials
Each student or student group should have:

  • Two 40-to-50 cm lengths of easily bendable wire that will hold a shape. 20-gauge wire used for floral arrangements works well and is available in many craft stores. (Warning: the ends of the wire can be dangerous. Have students wear goggles, and fold the ends of each wire back slightly to round them off).
  • A copy of the student version of the activity, including the Sample Cell Membrane Diagram
  • Scissors and paper
  • Scotch tape
  • Pencil

Suggestions

  • Have students read the “Research in the News” article from the Xenotransplantation issue of Snapshots as homework.
  • Before beginning the activity, briefly review with the students the unique structure of proteins, cell membranes, and antigen-antibody interactions in the immune response, as well as the diagrams in the student activity.
  • Have students work in small groups or pairs.
  • The students’ antigens should traverse both phospholipidlayers of the membrane and expose a unique shape on the outer membrane face.

 

The following is the Student Handout, also available in an editable and printer-friendly format:

Snapshots of Science & Medicine
Xenotransplants, Science Activity 1
Student Edition

You Look Familiar: Molecular Recognition in Immunity
Prepared by Fred Sculco, Noble and Greenough School, Dedham, Mass.

Introduction
Molecular recognition—the process by which one molecule binds only to its specific target and to no other molecule—is a key concept in biology.  Our own survival depends on millions of carefully choreographed molecular-recognition events occurring each and every second of our lives.  For example, the abilities of an enzyme to attach to its substrate, and a hormone to attach to its cellular receptor, and even a virus to attach to a host cell, all depend upon molecular recognition. (See Figure 1).

 

The immune system defends the body against foreign invaders. It, too, relies on molecular recognition. Specifically, the immune system must distinguish proteins and other molecules on the surfaces of our cells from molecules on the surfaces of cells that don’t belong.

Special proteins in the blood called antibodies are one way the immune system spots foreign invaders such as bacteria, fungi, protozoa, and viruses. Your body can make thousands of different antibodies. Each different antibody recognizes and binds to one specific foreign molecule, called an antigen.

Immune recognition also causes rejection of organ transplants. The recipient’s immune system recognizes proteins on the surfaces of the cell membranes of the transplanted organ as foreign. It then mounts an all-out war to rid the body of these foreign antigens, and in the process destroys the transplant. Controlling this destructive recognition process is the key to successful organ transplantation.

Scientists often rely on models in order to visualize how complex molecular structures such as antigens and antibodies recognize each other.  (You might remember that Watson and Crick built models to figure out the double-helix structure of DNA.) In this activity you’ll make a model of an antibody and its target antigen. In the process you’ll demonstrate that antibodies possess not only unique shapes that aid in attaching them to antigens but also unique patterns of charges, positive and negative areas resulting from electrons and protons in the molecule.  For an antibody to successfully bind its target antigen, both shape and charge must fit together.

A. Molecular Shapes of Antigens and Antibodies

    1. Find the sheet of paper entitled “Sample Cell Membrane” in this packet. The drawing of the membrane on this sheet shows only the phospholipid layers, with no other molecules embedded. Note, however, the gap in the membrane where you’ll supply a model protein antigen.

    2. Your teacher has given you two pieces of bendable wire. Use one of these to design a protein-antigen shape that will fit in the space on the membrane. (Warning: the ends of the wire can, literally, “put your eye out.” Be careful. Wear goggles, and bend the ends of each wire back slightly to round them off.) Your protein antigen should span both phospholipid layers of the membrane. The wire should also lie flat on the page—this is a two-dimensional model we’re building here. Using clear plastic tape, attach your shape to the sheet of paper in the space provided in the membrane. Figure 2 shows an example--but you can be a bit more adventurous in making your shape.

    3. Exchange the paper containing your antigen model with another team. Use your second piece of wire to create an antibody that would recognize and attach to the model antigen from the other team. Remember that antibodies have access only lto the part of the antigen that is poking outside the cell.

    Questions: Was the antibody molecule the other group designed to recognize your membrane antigen the same as you had envisioned? Is there only one specific shape that will attach and fit into the molecular shape of your antigen?

B. Molecular Charge—the Rest of the Story
The fact that several different molecules could have a shape that would make a reasonable fit onto the antigen molecule you made in Part A may seem confusing. Clearly, this would destroy the concept of specific molecular recognition. In biological systems, however, shape alone doesn’t determine whether two molecules will bind together. Small charged areas on molecules—created by slight separations between protons and electrons—also play an important part in molecular recognition. These charged areas create an array of positive (+) and negative (-) locations on the surface of the molecule. Because like charges repel each other, and opposite charges attract, the precise location of the charged areas on the antigen and the antibody make a huge difference in whether the two will stick together. It is the combination of both shape and charge that allows the specificity of molecular recognition events. 

    1. First you will add some negative and positive charges to the antigen molecules you made in your cell membrane.  Look over the shape of your antigen.  Using a pencil, draw five charged areas at random locations and in any arrangement you like. Don’t let other teams see the charge array you have drawn.

    2. Tape the antibody molecule you made in Part A onto a small piece of paper. Now use a pencil to draw five charged areas on your antibody.

    3. Again, exchange your charged antibody model with another team. Unless somebody peeked or got incredibly lucky, the charges on the model antibodies won’t correspond with the charges on the antigens.  Erase the incorrectly placed charges on the other team’s antibody, and draw new charges that would help the antibody and antigen bind.

    Questions: Which would bind more tightly, two molecules with highly complementary shapes but no surface charges, or these same two molecules that also have an array of complementary charges? How might scientists use knowledge of molecular shape and charge to design a molecule that could be used as a drug to interfere with the binding of an antigen and an antibody?