8 Entropic elasticity Elastin -- note linearity, small hysteresis. Normally found intertwined with collagen. Provides the “stretchiness” of tissues. Combination of single- molecule characteristics and microscale structure. 9 Image removed due to copyright considerations. See Figure 19-50 in: Alberts, Bruce, et al. Molecular Biology of the Cell. 4th ed. New York: Garland Publishing, 2002. Image may be viewed online at the NIH's PubMed Bookshelf. Image removed due to copyright considerations. See Figure 7.2:1 in: Fung, Y. C. Biomechanics: Mechanical Properties of Living Tissues. New York: Springer-Verlag, 1993 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books Canine aorta showing elastic fiber content. Histological cross-section artery stained for smooth muscle cells. Elastic response initially, then stiff, collagen response at high degrees of extension. H=hypertensive High wall stress leads to functional remodeling! of a diseased carotid 10 Image removed due to copyright considerations. See Figure 19-49 in: Alberts, Bruce, et al. Molecular Biology of the Cell. 4th ed. New York: Garland Publishing, 2002. Image may be viewed online at the NIH's PubMed Bookshelf. Image removed due to copyright considerations. Image removed due to copyright considerations. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books Lung parenchyma Mostly air, parenchyma mostly elastin and collagen. Effect of collagen at high degrees of extension Mostly linear response at small extensions Effect of surface tension of gas- liquid interface Proteoglycans (PGs) and glycosaminoglycans (GAGs) a) GLYCOSAMINOGLYCANS (GAGs) form gels i) polysaccharide chains of disaccharide units ii) too inflexible and highly charged to fold in a compact way iii) strongly hydrophilic iv) form extended conformations and gels v) osmotic swelling (charge repulsion) vi) usually make up less than 10% of ECM by weight vii) fill most of the ECM space viii) four main groups a. hyaluronan b. chondroitin sulfate and dermatin sulfate c. heparin sulfate and heparin d. keratin sulfate 11 Image removed due to copyright considerations Image removed due to copyright considerations b) Proteoglycans (PGs) i) form large aggregates ii) aggrecan is a large proteoglycan in cartilage iii) decorin is secreted by fibroblasts iv) PGs have varying amounts of GAGs. v) PGs are very diverse in structure and content vi) PGs and GAGs can also complex with collagen vii) secreted proteoglycans have multiple functions viii) some PGs are not secreted ix) PG/GAGs have important roles in cell-cell signaling 12 Image removed due to copyright considerations. See Figure 19-39 in: Alberts, Bruce, et al. Molecular Biology of the Cell. 4th ed. New York: Garland Publishing, 2002. Image may be viewed online at the NIH's PubMed Bookshelf. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books Quick-freeze, deep-etch TEM of cornea (100,000x) M. Johnson, J. Ruberti Striations can be seen on the collagen fibers. PGs can be seen bridging between the collagen fibers. 13 Image removed due to copyright considerations. Image removed due to copyright considerations. See Figure 19-37 in: Alberts, Bruce, et al. Molecular Biology of the Cell. 4th ed. New York: Garland Publishing, 2002. Image may be viewed online at the NIH's PubMed Bookshelf. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books 14 Image removed due to copyright considerations. See Figure 19-36 in: Alberts, Bruce, et al. Molecular Biology of the Cell. 4th ed. New York: Garland Publishing, 2002. Image may be viewed online at the NIH's PubMed Bookshelf. An aggrecan aggregate from fetal bovine cartilage. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books TISSUE Electrostatic: GAG other TISSUE NaCl Shear Modulus 16 Shear Modulus: (Dynamic @ 0.5Hz, 0.8% strain) Jin+, Macromolecules, 2001 Equilibrium G Dynamic G Dynamic Phase Like charge repulsion accounts for a large fraction (~50%) of the stiffness in tissues with high GAG content. These effects can be eliminated either by shielding (importance of Debye length -- BE.430!) with counter-ions or neutralization by changing pH. + + + + + + + + + + + + + + + + + + + + + + + + + + + + 17 Linear behavior up to fracture Relatively low toughness due to small fracture strain Leon, et al., 1998 Stress-Strain Behavior of KFE12 18 ADHESION PROTEINS a) fibronectin i) principal adhesion protein of connective tissues ii) fibronectin is a dimeric glycoprotein iii) fibronectin interacts with other molecules b) laminin i) found in basal laminae ii) form mesh-like polymers iii) has various binding sites iv) assembles networks of crosslinked proteins c) integrins i) cell surface receptor, for attachment of cells to ECM ii) family of transmembrane proteins iii) two subunits, alpha and beta iv) about 20 different integrins v) binding sites for ECM components vi) binding sites for the cytoskeleton and linkage to ECM 19