A Model for CD2/CD58-Mediated Adhesion Strengthening

Shao, Jin-Yu; Yu, Yan; Dustin, Michael L.

doi:10.1007/s10439-005-2504-5

Cited by 12 publications

(13 citation statements)

References 26 publications

(50 reference statements)

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“…A previous analysis of adhesion to bilayers containing the natural CD2 binding partner CD58 found a nonspecific contact area of [29]. We, however, find that the nonspecific contact area is driven to zero in all our fits.…”

Section: Discussioncontrasting

confidence: 67%

“…Moreover, in our experiments the small contact regions observed cause only small cellular deformations, and our target Jurkat T cells are substantially easier to deform than some other cell types, such as neutrophils and HL60 cells [28]. However, a recent study of the binding of Jurkat T cells to bilayers containing the natural CD2 ligand CD58 observed that the average contact area did not go to zero as the average number of bridging bonds went to zero [29], and a similar effect may be present in our data. To allow for this possibility, we include a nonspecific adhesion area into our contact area growth law, so that the total contact area is equal to the the nonspecific contribution plus a specific contribution proportional to the total number of bridging bonds:Dividing both sides by , we obtainThe parameter is the bridging bond density required to balance the repulsive force per unit area between the cell and the bilayer.…”

Section: Methodsmentioning

confidence: 51%

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A Biophysical Model of Cell Adhesion Mediated by Immunoadhesin Drugs and Antibodies

et al. 2011

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A promising direction in drug development is to exploit the ability of natural killer cells to kill antibody-labeled target cells. Monoclonal antibodies and drugs designed to elicit this effect typically bind cell-surface epitopes that are overexpressed on target cells but also present on other cells. Thus it is important to understand adhesion of cells by antibodies and similar molecules. We present an equilibrium model of such adhesion, incorporating heterogeneity in target cell epitope density, nonspecific adhesion forces, and epitope immobility. We compare with experiments on the adhesion of Jurkat T cells to bilayers containing the relevant natural killer cell receptor, with adhesion mediated by the drug alefacept. We show that a model in which all target cell epitopes are mobile and available is inconsistent with the data, suggesting that more complex mechanisms are at work. We hypothesize that the immobile epitope fraction may change with cell adhesion, and we find that such a model is more consistent with the data, although discrepancies remain. We also quantitatively describe the parameter space in which binding occurs. Our model elaborates substantially on previous work, and our results offer guidance for the refinement of therapeutic immunoadhesins. Furthermore, our comparison with data from Jurkat T cells also points toward mechanisms relating epitope immobility to cell adhesion.

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Section: Discussioncontrasting

confidence: 67%

Section: Methodsmentioning

confidence: 51%

A Biophysical Model of Cell Adhesion Mediated by Immunoadhesin Drugs and Antibodies

et al. 2011

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“…The 2D Kd measurement has subsequently been refined by modeling CD2 diffusion on cells (Dustin et al, 1997; Zhu et al, 2007; Zhu et al, 2006) and measuring the exclusion of freely diffusing molecules from the contact area (Bromley et al, 2001; Dustin et al, 2007b). The formation of contracts is dependent upon the 2D Kd more than on the kinetics of the interactions, making the 2D Kd an important parameter (Shao et al, 2005). …”

Section: Determination Of Two-dimensional Affinitymentioning

confidence: 99%

Supported bilayers at the vanguard of immune cell activation studies

Dustin¹

2009

Journal of Structural Biology

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Biological adhesion between cells is critical for development of multicellular organisms and for the function of the adaptive immune system of vertebrates. A gap in understanding of adhesion systems arises from the difficulty of collecting quantitative data on the molecular interactions underlying adhesion, which is typically studied by population statistics such as percent adhesion in the presence of empirically defined forces to separate less adherent cells. Supported lipid bilayers formed on glass surfaces offer a useful model system in which to explore some basic features of molecular interactions in adhesive contacts. We have exploited that lateral mobility of molecules in the supported planar bilayers and fluorescence microscopy to develop a system for measurement of two-dimensional affinities and kinetic rates in contact areas. Affinity measurements are based on a modified Scatchard analysis. Measurements of kinetic rates are based on fluorescence photobleaching after recovery at the level of the entire contact area. This has been coupled to a reaction-diffusion equation that allows calculation of on-and off-rates. We have found that mixtures of ligands in supported planar bilayers can effectively activate T lymphocytes and simultaneously allow monitoring of the immunological synapse. Recent studies in planar bilayers have provided additional insights into organization principles of cell-cell interfaces. Perennial problems in understanding cell-cell communication are yielding to quantitative measurements based on planar bilayers in areas of ligand driven receptor clustering and the role of the actin cytoskeleton in immune cell activation. A major goal for the field is determining quantitative rules involved in signaling complex formation.

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“…Since then, a good variety of mechanics models have been introduced, where the effects of fluid dynamics (Liu et al, 2006), fluid-structure interaction (Park et al, 2007), substrate pattern (Das and Du, 2008;Deshpande et al, 2008), thermodynamic considerations (Deshpande et al, 2008;Sarvestani, 2010) and other attributes (Nicolas et al, 2004;Ni and Chiang, 2007;Liu et al, 2007;Xu et al, 2009;Shao et al, 2005) were addressed. The kinetic model based on the study of the adhesion of a single giant vesicle onto a solid surface showed that the adhesion dynamics can be understood as a process of nucleation and growth (Boulbitch et al, 2001).…”

Section: Introductionmentioning

confidence: 99%