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Biological Materials

1. Elastin is a prototypical amorphous ECM molecule that is important for the elasticity of organs such as heart and skin. (22 pts)

a. Why is hydration required for elastin’s elastic effects? Briefly describe how water interactions and thermodynamics drive the properties of elastic recoil. (5 pts)

b. Do hydrophobic interactions exist? Why or why not? (2 pts)

c. Briefly describe the oiled-coil model of elasticity and how it relates to water interactions. What aspects of elastin cannot be explained by the oiled-coil model? (5 pts)

d. Briefly describe the phenomena of coacervation and the lower critical solution temperature (LCST). What intermolecular forces are required for this phase transition? (5 pts)

e. How can the phenomena of coacervation and LCST in elastin be applied to cancer therapy? (5 pts)

2. Collagens are crucial in maintaining the structural integrity of tissues by providing tensile strength. Since collagens are complex molecules, collagen-like peptides have been used widely. The (Gly-Pro-Hyp)₁₀ peptide was extensively studied due to its biophysical similarity to Collagen I. (23 pts)

a. List 3 major subclasses of collagen. How do differences in physical or chemical properties lead to their function and distribution in tissues? (6 pts)

b. Briefly describe the formation of the collagen triple helix and collagen fibrils. What environmental factors affect collagen fibril stability? How does stability under these factors compare to the (Gly-Pro-Hyp)₁₀ peptide? (5 pts)

c. How does the amino acid sequence of collagen contribute to its stability? How does the triple helix differ from an alpha helix? (5 pts)

d. Would the structure of the collagen triple helix be disrupted if glycine was substituted with a glutamine? Why or why not? (4 pts)

e. What is the importance of lysine residues in collagen fibrils? (3 pts) 

3. The poroelastic model can be used to describe the compressibility of various tissues. (20 pts)

a. Cartilage can be described by the biphasic poroelastic model. Briefly describe the components of the solid phase. (3 pts)

b. Which component of the solid phase accounts for the compressive strength of cartilage? Why? (5 pts)

c. Briefly describe the components of the fluid phase of cartilage. How does electrolyte concentration in the fluid impact the biomechanical properties of cartilage?  (3 pts)

d. Describe what would happen to the compressive strength of cartilage if the salt concentration in the body was significantly increased from physiological levels. What would happen if it was significantly decreased? (5 pts)

e. Name and describe a cellular component of cartilage that is not included in the poroelastic model. What does it contribute to the structure and function of cartilage? (2 pts)

f. Do current clinical strategies to repair or supplement cartilage (via surgery or hyaluronic acid injection) restore the biophysical characteristics of healthy cartilage? Why or why not? (2 pts)

4. Fibrin, a network polymer consisting of fibrinogen monomers, is a major component of blood clots. (20 pts)

a. What two critical enzymatic reactions are required for blood clot formation? Name the enzyme, substrate, product, and describe the biochemical functions of these reactions. (5 pts)

b. How does calcium deficiency impact either of the reactions you described in part a? (3 pts)

c. Why is the clotting cascade considered “autocatalytic”? (3 pts)

d. Describe the biophysical behavior of fibrin in a clot. How does it respond to shear deformation? Which component of its structure accounts for its viscoelastic relaxation? (5 pts)

e. Give an example of a function of transglutaminases in the body beyond the clotting cascade. (2 pts)

f. Celiac disease is an autoimmune disease that results in gluten intolerance and autoantibodies against tissue transglutaminase (which deamidates gluten). Why might your body erroneously produce an immune response to the product of a transglutaminase? (2 pts)

5. The lipid bilayer protects the cell and creates biochemical gradients. (15 pts)

a. How are lipid membranes affected by the following factors?

i. Temperature (2 pts)

ii. Degree of saturation (2 pts)

iii. Length of the fatty acid chain (2 pts)

iv. Presence of cholesterol (at low and high temperatures) (2 pts)

b. Lipid homeostasis is known to be affected in neurodegenerative diseases such as Alzheimer’s Disease and Huntington’s Disease, and it has been reported that cell membrane fluidity may be affected as a result. Design an experiment to test this hypothesis. What techniques could you use to characterize membrane fluidity? What controls would you include to confirm your hypothesis? (7 pts)