title: Elongated membrane tethers, individually anchored by high affinity α4β1/VCAM-1 complexes, are the quantal units of monocyte arrests.
abstract: The α4β1 integrin facilitates both monocyte rolling and adhesion to the vascular endothelium and is physiologically activated by monocyte chemoattractant protein (MCP-1). The current study investigated the initial events in the adhesion of THP-1 cells to immobilized Vascular Cell Adhesion Molecule 1 (VCAM-1). Using AFM force measurements, cell adhesion was shown to be mediated by two populations of α4β1/VCAM-1 complexes. A low affinity form of α4β1 was anchored to the elastic elements of the cytoskeleton, while a higher affinity conformer was coupled to the viscous elements of the cell membrane. Within 100 ms of contact, THP-1 cells, stimulated by co-immobilized MCP-1, exhibited a tremendous increase in adhesion to VCAM-1. Enhanced cell adhesion was accompanied by a local decoupling of the cell membrane from the cytoskeleton and the formation of long membrane tethers. The tethers were individually anchored by multiple α4β1/VCAM-1 complexes that prolonged the extension of the viscous tethers. In vivo, the formation of these membrane tethers may provide the quantal structural units for the arrest of rolling monocytes within the blood vessels.
authors.affiliation: Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Calvin
authors.initials: C
authors.lastname: Chu
authors.forename: Emrah
authors.initials: E
authors.lastname: Celik
authors.forename: Felix
authors.initials: F
authors.lastname: Rico
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Moy
mesh_terms: D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D018625:Microscopy, Atomic Force; D009000:Monocytes / Q000502:physiology*; D046912:Multiprotein Complexes / Q000378:metabolism*; D018709:Statistics, Nonparametric; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D039041:Integrin alpha4beta1; D046912:Multiprotein Complexes; D019010:Vascular Cell Adhesion Molecule-1