Measuring Receptor/Ligand Interaction at the Single-Bond Level: Experimental and Interpretative Issues

Zhu, Cheng; Long, Mian; Chesla, Scott E.; Bongrand, Pierre

doi:10.1114/1.1467923

Cited by 80 publications

(88 citation statements)

References 55 publications

(72 reference statements)

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“…This would result in a substantial increase in the relative population of the extended, high-affinity conformation compared to the less extended, low-affinity conformation in the presence of tensile force. Favoring the high-affinity conformation when force is applied (1) can give rise to catch bond behavior (4,6,33,35), (2) will dampen the increase in k off by applied force (8), (3) will stabilize rolling adhesive interactions in shear flow and may explain the finding that only certain classes of receptor-ligand pairs can support rolling interactions (10), and (4) can account for both force resistance and mechanotransduction by integrins during cell adhesion and migration (42). Adhesion in shear flow of K562 transfectants expressing wild-type I domains with type I or II TM domains.…”

Section: Discussionmentioning

confidence: 99%

“…Why rolling is so stable is imperfectly understood, although both cellular and molecular features contribute to the stability of rolling (1)(2)(3)(4)(5)(6)(7). One important factor as shear increases is the increase in the number of receptor-ligand bonds between the cell and the substrate, which compensates for faster bond dissociation (1).…”

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confidence: 99%

“…One important factor as shear increases is the increase in the number of receptor-ligand bonds between the cell and the substrate, which compensates for faster bond dissociation (1). Another factor is the mechanical stability of individual bonds, i.e., a low coefficient of increase in the rate of bond dissociation with an increase in force (2)(3)(4)(5)(6)8). Molecular specializations may be important, since among adhesion molecules, all selectin-ligand interactions and a subset of integrin-ligand interactions support rolling, whereas IgSF-IgSF and cadherin-cadherin interactions robustly support firm adhesion but not rolling adhesion (9).…”

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Importance of Force Linkage in Mechanochemistry of Adhesion Receptors

et al. 2006

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The α subunit-inserted (I) domain of integrin α L β 2 [lymphocyte function-associated antigen-1 (LFA-1)] binds to intercellular adhesion molecule-1 (ICAM-1). The C-and N-termini of the α I domain are near one another on the "lower" face, opposite the metal ion-dependent adhesion site (MIDAS) on the "upper face". In conversion to the open α I domain conformation, a 7 Å downward, axial displacement of C-terminal helix α 7 is allosterically linked to rearrangement of the MIDAS into its high-affinity conformation. Here, we test the hypothesis that when an applied force is appropriately linked to conformational change, the conformational change can stabilize adhesive interactions that resist the applied force. Integrin α I domains were anchored to the cell surface through their C-or N-termini using type I or II transmembrane domains, respectively. C-terminal but not N-terminal anchorage robustly supported cell rolling on ICAM-1 substrates in shear flow. In contrast, when the α L I domain was mutationally stabilized in the open conformation with a disulfide bond, it mediated comparable levels of firm adhesion with type I and type II membrane anchors. To exclude other effects as the source of differential adhesion, these results were replicated using α I domains conjugated through the N-or C-terminus to polystyrene microspheres. Our results demonstrate a mechanical feedback system for regulating the strength of an adhesive bond. A review of crystal structures of integrin α and β subunit I domains and selectins in high-and low-affinity conformations demonstrates a common mechanochemical design in which biologically applied tensile force stabilizes the more extended, high-affinity conformation.The ability of leukocytes to engage in a rolling adhesive interaction on endothelium is important as the first step in surveying endothelium for signals that trigger emigration. Rolling of leukocytes is driven by the hydrodynamic force of the bloodstream acting on an adherent cell and involves jerky stepwise movements of the cell that reflect receptor-ligand bond dissociation events. Rolling can be reproduced in vitro using leukocytes or transfectants in parallel wall flow chambers to which purified adhesion ligands are absorbed. Poised between firm adhesion and mechanically induced detachment, stable rolling requires bond dissociation under mechanical stress at the upstream edge of a cell to be balanced by the re-formation of bonds downstream in the adhesion zone between cell and substrate (1). Significantly, physiological rolling interactions are highly stable, both in vivo and in vitro, to alterations in surface ligand density and to the hydrodynamic force acting on the cell, which is proportional to the wall shear stress. † Supported by National Institutes of Health Grant HL48675. * To whom correspondence should be addressed. E-mail: springeroffice@cbr.med.harvard.edu. Phone: (617) Why rolling is so stable is imperfectly understood, although both cellular and molecular features contribute to the stability of rolling (1...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Importance of Force Linkage in Mechanochemistry of Adhesion Receptors

et al. 2006

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“…1C) to ensure ≥89% probability of single-bond formation as predicted by Poisson statistics (43). Only single-step dissociations were analyzed, to ensure that the lifetimes measured were time-to-dissociation of single bonds.…”

Section: Methodsmentioning

confidence: 99%

Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds

Lee

Lou

Wen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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As a key element in the cytoskeleton, actin filaments are highly dynamic structures that constantly sustain forces. However, the fundamental question of how force regulates actin dynamics is unclear. Using atomic force microscopy force-clamp experiments, we show that tensile force regulates G-actin/G-actin and G-actin/F-actin dissociation kinetics by prolonging bond lifetimes (catch bonds) at a low force range and by shortening bond lifetimes (slip bonds) beyond a threshold. Steered molecular dynamics simulations reveal force-induced formation of new interactions that include a lysine 113(K113):glutamic acid 195 (E195) salt bridge between actin subunits, thus suggesting a molecular basis for actin catch-slip bonds. This structural mechanism is supported by the suppression of the catch bonds by the single-residue replacements K113 to serine (K113S) and E195 to serine (E195S) on yeast actin. These results demonstrate and provide a structural explanation for actin catchslip bonds, which may provide a mechanoregulatory mechanism to control cell functions by regulating the depolymerization kinetics of force-bearing actin filaments throughout the cytoskeleton.single-molecule force spectroscopy | mechanotransduction | mechanosensing | nemaline myopathy T he actin cytoskeleton, primarily a force-bearing structure, controls the morphology, motility, and adhesion of the cell (1-4). Its core filamentous component, assembled from actin monomers via noncovalent interactions (5), undergoes rapid and controlled polymerization and depolymerization, allowing the dynamic reorganization of the actin cytoskeleton (1, 2).In cells, this dynamic process can be modulated by forces, and this is crucial to mechanosensitivity, mechanotransduction, and cellular adaptations to mechanical stresses (3, 6-8). For example, the assembly, stabilization, and reorganization of the actin stress fiber and the focal adhesion, where actin filaments constantly sustain tension, are induced by externally applied forces (9-12) dependent on myosin-generated contractility (4,8,13,14) and sensitive to substrate rigidity (3, 15, 16). These observations led us to investigate the molecular mechanism by which actin dynamics are regulated by force.The force-regulated kinetics of several molecular interactions important to adhesion and force-bearing functions of cells are governed by catch-slip bonds, in which the interaction is stabilized by tensile force in a low range and destabilized when force exceeds a threshold (17)(18)(19)(20)(21)(22). Various mechanisms, such as the allosteric model based on intramolecular conformational change under forces (23,24) and the sliding-rebinding model based on force-induced formation of new interactions due to intermolecular interface sliding (18,25), have been proposed to provide structural explanations for catch-slip bonds in different molecular interactions.Here we use atomic force microscopy (AFM) force-clamp experiments to determine how force regulates the off-rate of actin depolymerization and to elucidate the structural ...

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“…This is an issue complicated by many factors such as receptor valency, molecular clustering, and surface topography, as noted in the review by Zhu et al (61). For uniformly-distributed molecules and monovalent bindings, it has been shown that, as long as the adhesion frequency is low (less than 25%), adhesion is dominated mainly by single bonds (58,62).…”

Section: Applications Of the Matmentioning

confidence: 99%

Quantifying cell-adhesion strength with micropipette manipulation: principle and application

Shao¹

2004

Front Biosci

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Quantifying cell-adhesion strength is of great importance in biology and medicine. Cell-adhesion strength can be characterized by separating two adherent cells and determining the force required to do so, or by measuring the lifetime of a receptor-ligand bond that mediates cell adhesion. To this end, several micropipette-based experimental techniques that operate at both cellular and molecular levels have been developed over the past few decades. In this review, we provide an overview of three of these techniques, i.e., the step-pressure technique (SPT), the biomembraneforce probe (BFP), and the micropipette-aspiration technique (MAT). More detailed discussion will be given about the requirements and applications of the MAT.

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Measuring Receptor/Ligand Interaction at the Single-Bond Level: Experimental and Interpretative Issues

Cited by 80 publications

References 55 publications

Importance of Force Linkage in Mechanochemistry of Adhesion Receptors

Importance of Force Linkage in Mechanochemistry of Adhesion Receptors

Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds

Quantifying cell-adhesion strength with micropipette manipulation: principle and application

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