Contributions of molecular binding events and cellular compliance to the modulation of leukocyte adhesion.
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.
Department of Physiology and Biophysics, University of Miami School of Medicine, FL 33136, USA.
Ewa P
EP
Wojcikiewicz
Xiaohui
X
Zhang
Aileen
A
Chen
Vincent T
VT
Moy
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D004548:Elasticity / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D018625:Microscopy, Atomic Force; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D013314:Stress, Mechanical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D046911:Macromolecular Substances; D018799:Intercellular Adhesion Molecule-1; D013755:Tetradecanoylphorbol Acetate