Adhesion Energy of Receptor-Mediated Interaction Measured by Elastic Deformation

Moy, Vincent T.; Yi, Jae-Seon; Hillmann, Thomas; Lehmann, Horst; Sano, Tsuyoshi

doi:10.1016/s0006-3495(99)77322-4

Cited by 61 publications

(58 citation statements)

References 35 publications

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“…According to theoretical estimates for a protein complex that spans about 20 nm η = 1.2×10 19 ♯ m 2 M [Bell, 1978]. Studies employing protein-coated beads report η = 8 × 10 24 ♯ m 2 M [Moy et al, 1999] and η = 10 22 ♯ m 2 M [Kuo & Lauffenburger, 1993]. The lower η value is corroborated by measurements of the 2-dimensional dissociation constant for the LFA-3/CD2 adhesion pair that were carried out using cells instead of beads [Dustin et al, 1996].…”

Section: Ligand Engagement Is Not Sufficient For Integrin Activationmentioning

confidence: 99%

Integrin activation—the importance of a positive feedback

Iber¹,

Campbell

2006

Bull. Math. Biol.

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1Integrins mediate cell adhesion and are essential receptors for the development and functioning of multicellular organisms. Integrin activation is known to require both ligand and talin binding and to correlate with cluster formation but the activation mechanism and precise roles of these processes are not yet resolved. Here mathematical modeling, with known experimental parameters, is used to show that the binding of a stabilizing factor, such as talin, is alone insufficient to enable ligand-dependent integrin activation for all observed conditions; an additional positive feedback is required.Keywords Talin, integrin, receptor activation, Master equation, positive feedback 2 IntroductionIntegrins, large membrane-spanning heterodimeric proteins, were so named for their ability to link the extracellular and intracellular skeletons [Tamkun et al., 1986]. As an important class of cell adhesion receptors they participate in a wide-range of biological interactions, including development, tissue repair, angiogenesis, inflammation and hemostasis [Horwitz & Webb, 2003]. Cell adhesion and detachment as well as controlled actin polymerisation inside the cell are of particular importance in cell migration. The speed of cell movement depends on the density of integrins and ligands as well as their affinity of binding [Palecek et al., 1997]. Integrins are key components of focal adhesions, dynamic multi-protein complexes that are involved in the regulation of cell adhesion and migration. Focal adhesions [Zamir & Geiger, 2001] provide a physical link between integrins and the actin cytoskeleton as well as sites for signal transduction into the cell interior. Information about identified interactions and players in these complexes is ever-increasing but our overall understanding of how the ensemble works remains relatively poor.According to the current model of integrin activation, ligand binding shifts the equilibrium between different integrin conformations to the active one [Hynes, 2002]. The two extreme conformations of this allosteric protein are a bent or 'closed' conformation which represents the low affinity state for ligand and an 'open' conformation that will bind with high affinity to ligand. Conformational changes in the extracellular domain affect the cytoplasmic tails, which are separated in the open conformation but not in the closed. Separation of the cytoplasmic domains promotes their interaction with cytoskeletal and signal transduction molecules, and thus the activation of integrins and downstream signaling. The conformational equilibrium can be influenced both by ligand binding to the extracellular domain (outside-in signaling) and by binding of cytoplasmic proteins to the separated cytoplasmic domains (inside-out signaling). As well as changes in affinity induced by structural changes, integrins can also modulate their avidity by clustering, thus changing the valency of their interactions with ligand [Carman & Springer, 2003].Previous theoretical studies have addressed the mechanism of integrin clustering...

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Section: Ligand Engagement Is Not Sufficient For Integrin Activationmentioning

confidence: 99%

Integrin activation—the importance of a positive feedback

Iber¹,

Campbell

2006

Bull. Math. Biol.

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“…More recent developments in AFM now allow the detection of molecular recognition events between single molecules using ligands attached to AFM tips for the recognition of receptors bound on rigid surfaces (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). By monitoring the cantilever def lection during approach-retraction cycles (i.e., forcevolume͞force-distance curves) at a constant (lateral) position on the sample, unbinding forces (i.e., the maximum force at the moment of receptor-ligand detachment) have been determined for various ligand-receptor pairs, including biotin-avidin (13,14,21), DNA bases (15), antibody-antigen (16)(17)(18)(19)(20)(21)(22), and cellrecognition proteins (23).…”

mentioning

confidence: 99%

Combining constitutive materials modeling with atomic force microscopy to understand the mechanical properties of living cells

McElfresh

Baesu

Balhorn

et al. 2002

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

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The goal of this work is to study the properties of living cells and cell membranes by using atomic force microscopy. During atomic force microscopy (AFM) measurement, there is a strong mechanical coupling between the AFM tip and the cell. The purpose of this paper is to present a model of the overall mechanical response of the cell that allows us to separate out the mechanical response of the cell from the local surface interactions we wish to quantify. These local interactions include recognition (or binding) events between molecules bound to an AFM tip (e.g., an antibody) and molecules or receptors on the cell surface (e.g., the respective antigen). The computational model differs from traditional Hertzian contact models by explicitly taking into account the mechanics of the biomembrane and cytoskeleton. The model also accounts for the mechanical response of the living cell during arbitrary deformation. The indentation of a bovine sperm cell is used to test the validity of this model, and further experiments are proposed to fully parameterize the model.

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“…Cells are complex and dynamic by nature and cell adhesion, apart from ligand-receptor binding, is contributed by receptor-CSK interactions as well as CSK reorganization 23 . In fact, altering the expression of a candidate protein does not necessarily imply that the function of the cell will correspond.…”

Section: Analysis Of Retraction F-d Curves Obtained From Cell-to-celmentioning

confidence: 99%

“…In addition, the adhesive behaviour of cell with other surfaces is crucial for the biocompatibility of implants 7 . Cell adhesion is a dynamic process, which is controlled by the binding of adhesion molecules on the cell surface 23 . However, as a living system, cells have a highly complex organisational architecture that exhibits complicated mechanical and adhesive behaviours.…”

Section: Introductionmentioning

confidence: 99%

Nanomechanical Investigation of Soft Biological Cell Adhesion using Atomic Force Microscopy

et al. 2014

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Mechanical coupling between living cells is a complex process that is important for a variety of biological processes. In this study the effects of specific biochemical treatment on cell-to-cell adhesion and single cell mechanics were systematically investigated using Atomic Force Microscopy (AFM) Single Cell Force Spectroscopy. Functionalised AFM tipless cantilevers were used for attaching single suspended cells that were brought in contact with substrate cells. Cell-to-cell adhesion parameters, such as maximum unbinding force (F max ) and work or energy of detachment (W D ), were extracted from the retraction force-displacement (F-d) curves. AFM indentation experiments were performed by indenting single cells with a spherical microbead attached to the cantilever. Hertzian contact model was applied to determine the elastic modulus (E). Following treatment of the cells with neutralising antibody for epithelial (E)-cadherin, F max was increased by 25%, whereas W D decreased by 11% in response to a 43% increase in E. The results suggest that although the adhesion force between cells increased after treatment due to higher ligand-receptor binding, the energy of adhesion was decreased due to the reduced displacement separation as manifested by the loss of elastic deformation. Conclusively, changes in single cell mechanics are important underlying factors contributing to cell-to-cell adhesion and hence cytomechanical characterization is critical for cell adhesion measurements.

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Adhesion Energy of Receptor-Mediated Interaction Measured by Elastic Deformation

Cited by 61 publications

References 35 publications

Integrin activation—the importance of a positive feedback

Integrin activation—the importance of a positive feedback

Combining constitutive materials modeling with atomic force microscopy to understand the mechanical properties of living cells

Nanomechanical Investigation of Soft Biological Cell Adhesion using Atomic Force Microscopy

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