Cell Adhesion ? Structural Integrity ? External Sensing ?Migration ? Regulation of Transport ? Communication Lodish Chapter 22 Kamm Chapter 2 Overview of the types of molecules that bind cells to each other and to the extracellular matrix Cell adhesion molecules and their characteristics Family Location and/or Ligands Comments function recognized integrins focal adhesions, (E) fibronectin, relatively low hemi-desmosomes, leukocy te collagen, laminin, immunoglobulins, affinities (K D ~ 10 -6 -10 -8 ("spreading") (I) actin filaments mol/liter) adhesion, primarily cell-matrix adhesion but also in some cell-cell adhesions selectins circulating cells and carbohydrates require Ca 2+ endothelial cells, "rolling" adhesion Ig superfamily important in integrins, (immunoglobulin) cadherens immune response adherens junctions, homophillic (E) homophillic, require Ca 2+ desmosomes (I) actin filaments, intermediate filaments RD Kamm 2003 Adhesion complexes Junction type Function Extracellular or adjacent cell attachment Intracellular attachment Adherens structural, cell-cell or cell- matrix ECM proteins or cadherins in actin filaments Desmosome structural, cell-cell adjacent cell cadherin intermediate filaments Hemidesmosome structural, cell-matrix basal lamina via intermediate Focal adhesions Tight junction structural, cell-matrix regulate transport between cells and along cell membrane integrins ECM proteins via integrins filaments actin filaments Gap junctions cell-cell communication via ion and small molecule chann els formed by connex in subun its exchange Table 2. Adhe sion co mplexes. Gap junctions allow small molecules to pass between adjacent cells Image removed due to copyright considerations. See Orsello, C.E., D. A. Lauffenburger and D. A. Hammer. “Molecular properties in cell adhesion: a physical and engineering perspective.” TRENDS in Biotechnology, Vol. 19 No. 8 (August 2001). Selectins and other CAMs participate in leukocyte extravasation Integrins mediate weak cell-matrix and cell-cell interactions Cell-matrix adhesion is modulated by changes in the activity and number of integrins Image removed due to copyright considerations. See [Lodish] Table 22-2. PubMed URL: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.table.6528 De-adhesion factors promote cell migration and can remodel the cell surface Integrin-containing junctions connect cells to the substratum Image removed due to copyright considerations. See [Lodish] Figure 22-9. PubMed URL: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.figgrp.6533 Integrin-containing junctions connect cells to the substratum Focal adhesions: clusters of receptors Image removed due to copyright considerations. See [Lodish] Figure 22-10. PubMed does not have this image. Figure 22-10 Comparison to JKR theory for adhesion Image removed due to copyright considerations. Ligand-receptor system: iminobiotin- avidin Moy et al. Biophys J. 1999 Images removed due to copyright considerations. See Fig. 5 and Table 2 in Chen, Shuqi and Timothy A. Springer. “Selectin receptor-ligand bonds: Formation limited by shear rate and dissociation governed by the Bell model.” PNAS v98(3): 950-5 (Jan 30 2001). 2000). Images removed due to copyright considerations. See Fig. 1, Fig. 3 and Table 1 in Chang, Kai-Chien, David F. J. Tees, and Daniel A. Hammer. “The state diagram for cell adhesion under flow: Leukocycte rolling and firm adhesion.” PNAS v97(21): 11262 (Oct. 10,