1. 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 1 st and 2 nd 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 AN UNDERGRADUATE 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 2 nd 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 assigned January 23: Report guidelines handed out January 30: Topic officially chosen by group February 13: Preliminary bibliography due February 25: Preliminary outline due March 17: Preliminary 5 minute presentations April 2: Final outline or rough draft due April 16: Final group report due Finals week: 20 minute group presentations