Contributions of molecular binding events and cellular compliance to the modulation of leukocyte adhesion

J Cell Sci. 2003 Jun 15;116(Pt 12):2531-9. doi: 10.1242/jcs.00465. Epub 2003 May 6.


The interaction of leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is central to the regulation of adhesion in leukocytes. In this report, we investigated the mechanisms by which phorbol myristate acetate (PMA) promotes LFA-1-dependent cell adhesion. The adhesion of PMA-stimulated cells to immobilized ICAM-1 was quantified in direct force measurements acquired by atomic force microscopy (AFM). Enhanced adhesion of PMA-stimulated cells to immobilized ICAM-1 stemmed from an increase in the number of LFA-1-ICAM-1 complexes formed between the two apposing surfaces on contact, rather than by affinity modulation of LFA-1. Single molecule force measurements revealed that the force spectrum of the LFA-1-ICAM-1 complex formed by PMA-stimulated cells is identical to the force spectrum of the complex formed by resting cells. Thus, PMA stimulation does not modify the mechanical strength of the individual LFA-1-ICAM-1 interaction. Instead, the enhanced cell adhesion of PMA-stimulated cells appears to be a complex process that correlates with changes in the mechanical properties of the cell. We estimate that changes in the elasticity of the cell gave rise to a more than 10-fold increase in cell adhesion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cell Adhesion Molecules / drug effects
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Cell Membrane / metabolism*
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / physiology*
  • Elasticity / drug effects
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Leukocytes / metabolism*
  • Lymphocyte Function-Associated Antigen-1 / drug effects
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Macromolecular Substances
  • Mice
  • Microscopy, Atomic Force
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Stress, Mechanical
  • Tetradecanoylphorbol Acetate / pharmacology


  • Cell Adhesion Molecules
  • Lymphocyte Function-Associated Antigen-1
  • Macromolecular Substances
  • Intercellular Adhesion Molecule-1
  • Tetradecanoylphorbol Acetate