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.

[1]  M. Shimaoka,et al.  Conformational regulation of integrin structure and function. , 2002, Annual review of biophysics and biomolecular structure.

[2]  P K Hansma,et al.  Measuring the viscoelastic properties of human platelets with the atomic force microscope. , 1996, Biophysical journal.

[3]  V. Moy,et al.  Mechanical properties of L929 cells measured by atomic force microscopy: effects of anticytoskeletal drugs and membrane crosslinking. , 2006, Scanning.

[4]  Michael Loran Dustin,et al.  Role of lymphocyte adhesion receptors in transient interactions and cell locomotion. , 1991, Annual review of immunology.

[5]  B G De Grooth,et al.  Biomolecular interactions measured by atomic force microscopy. , 2000, Biophysical journal.

[6]  J. Bechhoefer,et al.  Calibration of atomic‐force microscope tips , 1993 .

[7]  Colin R. F. Monks,et al.  Three-dimensional segregation of supramolecular activation clusters in T cells , 1998, Nature.

[8]  R. Liddington,et al.  Cellular Activation of Leukocyte Function-Associated Antigen-1 and Its Affinity Are Regulated at the I Domain Allosteric Site , 2001, The Journal of Immunology.

[9]  W F Heinz,et al.  Spatially resolved force spectroscopy of biological surfaces using the atomic force microscope. , 1999, Trends in biotechnology.

[10]  Ximing Zhou,et al.  Macrophage-enriched Myristoylated Alanine-rich C Kinase Substrate and Its Phosphorylation Is Required for the Phorbol Ester-stimulated Diffusion of β2 Integrin Molecules* , 2000, The Journal of Biological Chemistry.

[11]  S. Bromley,et al.  The immunological synapse: a molecular machine controlling T cell activation. , 1999, Science.

[12]  J. R. Huth,et al.  NMR and mutagenesis evidence for an I domain allosteric site that regulates lymphocyte function-associated antigen 1 ligand binding. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Evan Evans,et al.  Chemically distinct transition states govern rapid dissociation of single L-selectin bonds under force , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Timothy A. Springer,et al.  The dynamic regulation of integrin adhesiveness , 1994, Current Biology.

[15]  Junichi Takagi,et al.  Locking in alternate conformations of the integrin αLβ2 I domain with disulfide bonds reveals functional relationships among integrin domains , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  B. Seed,et al.  αLβ2 Integrin/LFA-1 Binding to ICAM-1 Induced by Cytohesin-1, a Cytoplasmic Regulatory Molecule , 1996, Cell.

[17]  Michael Loran Dustin,et al.  Low affinity of cell surface lymphocyte function-associated antigen-1 (LFA-1) generates selectivity for cell-cell interactions. , 1997, Journal of immunology.

[18]  M. Benoit.  Cell adhesion measured by force spectroscopy on living cells. , 2002, Methods in cell biology.

[19]  Manfred Radmacher,et al.  Direct, high-resolution measurement of furrow stiffening during division of adherent cells , 2001, Nature Cell Biology.

[20]  Hermann E. Gaub,et al.  Discrete interactions in cell adhesion measured by single-molecule force spectroscopy , 2000, Nature Cell Biology.

[21]  S. Singer,et al.  The PMA-induced specific association of LFA-1 and talin in intact cloned T helper cells. , 1990, The Journal of molecular and cellular immunology : JMCI.

[22]  V. Moy,et al.  Direct evidence for two affinity states for lymphocyte function-associated antigen 1 on activated T cells. , 1993, The Journal of biological chemistry.

[23]  B. Seed,et al.  Alpha L beta 2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule. , 1996, Cell.

[24]  R. Waugh,et al.  A microcantilever device to assess the effect of force on the lifetime of selectin-carbohydrate bonds. , 2001, Biophysical journal.

[25]  V. Moy,et al.  Force spectroscopy of the leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. , 2002, Biophysical journal.

[26]  Timothy A. Springer,et al.  Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1) , 1987, Cell.

[27]  N. Hogg,et al.  T cell adhesion to intercellular adhesion molecule-1 (ICAM-1) is controlled by cell spreading and the activation of integrin LFA-1. , 1996, Journal of immunology.

[28]  Y. Nishizuka,et al.  Protein kinase C and T cell activation. , 1990, European journal of biochemistry.

[29]  N. Hogg,et al.  Regulation of leukocyte integrin function: Affinity vs. avidity , 1996, Journal of cellular biochemistry.

[30]  J. Hoh,et al.  Surface morphology and mechanical properties of MDCK monolayers by atomic force microscopy , 1996 .

[31]  N. Hogg,et al.  LFA-1–mediated Adhesion Is Regulated by Cytoskeletal Restraint and by a Ca2+-dependent Protease, Calpain , 1998, The Journal of cell biology.

[32]  J. Woska,et al.  Characterization of molecular interactions between intercellular adhesion molecule-1 and leukocyte function- associated antigen-1. , 1996, Journal of immunology.

[33]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[34]  H. Arakawa.  [Force spectroscopy]. , 2004, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[35]  C. Turck,et al.  A role for the actin-bundling protein L-plastin in the regulation of leukocyte integrin function. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[36]  V. Moy,et al.  Cross-linking of cell surface receptors enhances cooperativity of molecular adhesion. , 2000, Biophysical journal.

[37]  Timothy A. Springer,et al.  Adhesion receptors of the immune system , 1990, Nature.

[38]  V. Moy,et al.  The accessory function of murine intercellular adhesion molecule-1 in T lymphocyte activation. Contributions of adhesion and co-activation. , 1991, Journal of immunology.

[39]  C. Figdor,et al.  Avidity regulation of integrins: the driving force in leukocyte adhesion. , 2000, Current opinion in cell biology.

[40]  T. Springer,et al.  The requirement for lymphocyte function-associated antigen 1 in homotypic leukocyte adhesion stimulated by phorbol ester , 1986, The Journal of experimental medicine.