Chemistry of biological adhesion

PHYS 65

Deborah Leckband, leckband@uiuc.edu, Department of Chemistry, University of Illinois, 600 South Mathews Ave., Urbana, IL 61801, Marco Bayas, Departamento de Física y Astronomía, Escuela Politécnica Nacional, Casilla 17 01 2759, Quito, Ecuador, Alice Kearney, Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom, Anton van der Merwe, anton.vandermerwe@pathology.oxford.ac.uk, Sir William Dunn School of Pathology, Oxford University, Oxford, OX1 3RE, United Kingdom, and Klaus Schulten, Department of Physics and Beckman Institute, U. of Illinois at Urbana-Champaign, Urbana, IL 61801.
Cell-cell adhesion in vivo is determined primarily by large numbers of protein binders on cell membranes. One fundamental question is how bond chemistry determines the strength of the intercellular junctions. In addition, while much is known about the physics determining strengths of single (isolated) noncovalent bonds, cell adhesion is rarely mediated by single proteins. However, no analyses have explored how molecular properties scale the collective adhesive behavior of multiple bonds in parallel between membrane surfaces. This talk describes a multi-scale investigation of the adhesive strength of multiple protein bonds in parallel and the correlation of the adhesion with the thermodynamic and kinetic properties of the bonds. Atomistic simulations identified critical load bearing amino acids at the protein-protein interfaces. Mutants generated on the basis of these simulations were characterized thermodynamically and kinetically. Subsequent molecular force measurements of protein-mediated intermembrane adhesion in turn established correlations between the thermodynamic and kinetic properties and the measured adhesion. These findings suggest surprising similarities between the strengths of single bonds and strength of adhesion mediated by multiple bonds in parallel.