Course Topics Cooperative Learning

In Spring 2004 I developed a new undergraduate course in “Extracellular Matrix.”

• Designed to be a senior level elective for our “Biomaterials and Biomechanics” and “Cellular and Molecular Engineering” pathways

• 1 semester course, 3 credit hours

• 21 students enrolled

• 8 undergraduates (7 seniors and 1 junior)

• 1 of the undergraduates was from the Biosciences Department

• 13 1st and 2nd year graduate students

• 1 graduate student was from another school (Baylor College of Medicine program in Medical Physics)

The course was taught by myself and 1 teaching assistant (1-2 lectures)

Course topics:

GAGs and PGs were studied in several lectures.

Outline of lecture material:

1. Definitions and building blocks

• GAGs

• PGs

2. Types of GAGs and PGs

• Structure and definition of modifying groups

• Function

• Distribution

• Biomechanics

3. How GAGs and PGs are studied

4. Biological vs. biomechanical roles

5. How PGs are different from glycoproteins

6. GAG chain synthesis

• Sulfated/modified GAGs

• Hyaluronan

7. PG synthesis and aggregation

8. Matrix-matrix interactions: Decorin and Lumican in Collagen Fibrillogenesis In Vitro

9. Lumican and Fibromodulin knockout mice and Collagen Fibrillogenesis In Vivo

10.Elastin and Versican / Chondroitin Sulfate

Learning goals discussed at the end of class:

1. Define the basic GAG structure

2. Define the 4 GAG classes

3. Describe the basic structure and variability of PGs

4. Explain how PG and GAG structure affects tissue biomechanics

5. Explain the biological role of PGs

6. Describe the order in which GAG chain modifications occur

7. Speculate how GAG disaccharide sulfation plays a role in limiting chain size

8. Explain how HA synthesis is different from other GAGs

9. Describe the different binding sites of DSPGs and KSPGs on fibrillar collagen.

10.Describe the advantages and disadvantages of in vitro and in vivo studies for examining matrix interactions.

11.Differentiate between the PG inhibition of collagen and the PG inhibition of elastin.

• What part of the PG is involved?

12.Describe the sections of the versican core protein.

• Which variants exist normally in tissues?

• Which sections/parts are responsible for inhibiting elastin, and how?

FeedbackFocus on PGs

TEACHING PROTEOGLYCAN BIOLOGY AND BIOMECHANICS IN ANUNDERGRADUATE EXTRACELLULAR MATRIX COURSE

K. Jane Grande-Allen, Ph.D.Department of Bioengineering, Rice University, Houston, TX, USA,

Students’ questions about PGs and GAGs

• “I’m not very good at chemistry and nomenclature. What is the function of these modifying groups and how can I tell them apart?”

• “Are all HSPGs the same PG?”

• “Is the large HSPG of basement membrane perlecan?”

• “If the decorin concentration was found to be elevated in …., will that make the tissue failure strength increase or decrease?”

• “Why do all these literature papers have opposite data about the trends in GAGs and PGs?”

• “What is the difference between aggrecan and an aggregate?”

• “How specifically does decorin inhibit collagen?”

• “How are sugars made?”

Feedback from Formal/Informal Course Evaluations

• Most of the students felt that the cell biology information was too redundant with their previous coursework.

• One student who had never had this material before, however, really appreciated it. I think that I will have outside-class review sessions in the future.

• The receptor-ligand and enzyme kinetics sections were not very popular.

• Revise these to relate them more clearly to tissue degradation and mechanotraduction

• Almost all students wanted more information on PGs, GAGs, and glycoproteins

• Students requested more material about matrix production, turnover, and remodeling

• Students want more in-depth information on biochemistry techniques

• Next year, do the final presentation before the final report is due

Part 1: Cell Biology Basis for Matrix Mechanics

Course Overview, Cell structure and organization

Cell phenotypes, Cellular responses to stresses

Cell Signaling and Communications

Cell Binding/Adhesions, Integrins

Receptor-Ligand Binding Models

Mechanical Properties of Cells

Part 2: Extracellular Matrix Constituents and Analysis

Collagen Structure and Mechanics

Elastin Structure and Mechanics

Proteoglycans/GAGs Structure and Mechanics

Glycoproteins Structure and Mechanics (Basement Membranes)

Biology/Biochemistry Techniques

Part 3: The Roles of Matrix in Tissues and Organs

Tissue Organization, Tissue Types, Cell lineages

Tissue Origins, Cells, Functions, Examples of Connective Tissues

Definition and Organization of Organs

Experimental Techniques for tissue mechanics

Part 4: Matrix Production, Turnover, and Degradation

Cellular Production of Matrix

Matrix-Matrix Interactions

Tissue Degradation

Michaelis-Mentin Models of enzyme-substrate kinetics

Tissue remodeling: variations, impact on mechanics

Tissue Aging

We formed teams/discussion groups in the 2nd class.

• Students had the same group partners all semester

• We had several group discussions on various topics, for example:• Design devices to stretch cells for

mechanotransduction studies• Discuss potential cellular responses to

signaling from the ECM• Test and discuss various hand lotions. What

do they really need to do for skin? Do you trust their claims? Design a skin treatment and how you would market it.

• How would you characterize a certain tissue biomechanically and construct a constitutive model to explain its behavior?

• Teams were encouraged to study together for quizzes and the midterm exam.• One quiz was taken in groups of 3.

• The teams worked on group reports all semester.

Potential Topics: (these topics were chosen) 1. Heritable disorders of connective tissue. 2. Discuss how ECM components is/are different in

the developing fetus vs. juvenile and adult matrix.3. Normal aging of the ECM and the accelerated

aging process in premature aging syndromes.4. Mechanical forces in the developing fetus and the

three main embryonic tissue types. 5. ECM in the endocrine system or lymphatic system. 6. ECM in the female reproductive system. 7. How tissues (fresh or from a tissue bank) are

converted into ECM scaffolds for tissue engineering. 8. Laboratory (as opposed to cell biology) approaches

to the artificial creation of ECM. 9. ECM and the structure and function of the nervous

system, including the brain. 10. ECM of invertebrates, insects, or plants.

Milestones:January 14: Groups members assignedJanuary 23: Report guidelines handed outJanuary 30: Topic officially chosen by groupFebruary 13: Preliminary bibliography dueFebruary 25: Preliminary outline dueMarch 17: Preliminary 5 minute presentationsApril 2: Final outline or rough draft due April 16: Final group report dueFinals week: 20 minute group presentations