Binding cooperativity of membrane adhesion receptors

Krobath, Heinrich; Różycki, Bartosz; Lipowsky, Reinhard; Weikl, Thomas R.

doi:10.1039/b902036e

Cited by 76 publications

(155 citation statements)

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“…A different scaling is expected if the binding rate depends on the average position and fluctuations of the free membrane between anchoring points. If the on-rate obeys detailed balance, one expects r b,eq~r0 2 in the absence of a pressure difference (20,21). As discussed in the following sections, the results of micropipette experiments are consistent with a linear scaling s*~r 0 .…”

Section: Methodsmentioning

confidence: 61%

“…This assumption allows us to disregard membrane fluctuations between attachment points, and yields a simple analytical form for the unbinding transition. However, it does not capture binding cooperativity occurring due to the smoothing of membrane fluctuations near attachment points (19)(20)(21)(22)(23). Two relevant dimensionless quantities characterize the mechanics of the linkers: the kinetic ratio, c, and the ratio of the force on the membrane to an intrinsic force scale of the linkers, a, with ch k 0 off k on and ah sd r 0 k B T :…”

Section: Methodsmentioning

confidence: 99%

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Model for Probing Membrane-Cortex Adhesion by Micropipette Aspiration and Fluctuation Spectroscopy

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Casademunt

Brugués

et al. 2015

Biophysical Journal

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We propose a model for membrane-cortex adhesion that couples membrane deformations, hydrodynamics, and kinetics of membrane-cortex ligands. In its simplest form, the model gives explicit predictions for the critical pressure for membrane detachment and for the value of adhesion energy. We show that these quantities exhibit a significant dependence on the active acto-myosin stresses. The model provides a simple framework to access quantitative information on cortical activity by means of micropipette experiments. We also extend the model to incorporate fluctuations and show that detailed information on the stability of membrane-cortex coupling can be obtained by a combination of micropipette aspiration and fluctuation spectroscopy measurements.

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Section: Methodsmentioning

confidence: 61%

Section: Methodsmentioning

confidence: 99%

Model for Probing Membrane-Cortex Adhesion by Micropipette Aspiration and Fluctuation Spectroscopy

Alert

Casademunt

Brugués

et al. 2015

Biophysical Journal

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“…While the accumulation itself arises purely because of thermodynamic reasons, 4 membrane deformation and/or fluctuation mediated correlations between bonds aid in their compaction and organization. [13][14][15] In the present case, though the receptors are bulky and hence slowly diffusing, when present in sufficient numbers (>2% of the lipids in the supported membrane are functionalized), they are able to fill the adhesion disc to the limit of geometrical close packing during the initial growth of the domain. At intermediate concentrations (0.5% $ c r < 2% functionalized lipids), the filling is homogeneous but the limit of geometrical close packing is not reached.…”

Section: Resultsmentioning

confidence: 99%

Inter-membrane adhesion mediated by mobile linkers: Effect of receptor shortage

et al. 2011

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Giant unilamellar vesicles (GUVs) adhering to supported bilayers were used as a model system to mimic ligand-receptor mediated cell-cell adhesion. We present the effect of varying the concentration of receptors (neutravidin on the bilayer) and ligands (biotin on the vesicle) on GUV adhesion and the organization of receptors in the adhesion zone. At high concentrations of both ligands and receptors, the adhesion is strong, all the available membrane is adhered and receptors are accumulated under the adhered membrane up to the geometrical limit of close packing. At low concentrations of receptors (<0.5%), and an arbitrary concentration of ligands ($0.1%), adhesion does not proceed to completion: the membrane is only partially bound and parts of it still fluctuate. The receptors tend to accumulate under the adhered membrane but the filling is partial. Receptors get jammed and form clusters with fractal like shapes along the rim of the adhered vesicle in such a way that the annular cluster prevents further filling of the adhesion disc. We characterize the filling in terms of a compaction factor and the final concentration. Interestingly, the closing of the ring of jammed clusters switches the interior of the adhesion disc from one thermodynamic ensemble to another. In the new ensemble the receptors sealed within the adhesion disc are mobile but their number is fixed. Under such conditions, the usually strong neutravidin/biotin bond is weak. The incomplete adhesion state can be attributed to a combination of the effects of diffusion, jamming and the competition of enthalpy and entropy on bond formation. The formation of jammed receptor clusters reported here represents a new mechanism that influences membrane adhesion.

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“…nAT n ðN R − n + 1ÞðN L − n + 1ÞT n−1 [19] because the transition numbers N + n−1 and N − n are identical in equilibrium. For our simulations with a single receptor and a single ligand, the maximumlikelihood estimators for the on-and off-rate constants thus are k For large numbers N R and N L of receptors and ligands and states with n ' n receptor-ligand bonds where n is the average number of bonds, Eq.…”

Section: Model and Methodsmentioning

confidence: 99%

Binding constants of membrane-anchored receptors and ligands depend strongly on the nanoscale roughness of membranes

Lipowsky

Weikl

2013

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

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121

144

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Cell adhesion and the adhesion of vesicles to the membranes of cells or organelles are pivotal for immune responses, tissue formation, and cell signaling. The adhesion processes depend sensitively on the binding constant of the membrane-anchored receptor and ligand proteins that mediate adhesion, but this constant is difficult to measure in experiments. We have investigated the binding of membrane-anchored receptor and ligand proteins with molecular dynamics simulations. We find that the binding constant of the anchored proteins strongly decreases with the membrane roughness caused by thermally excited membrane shape fluctuations on nanoscales. We present a theory that explains the roughness dependence of the binding constant for the anchored proteins from membrane confinement and that relates this constant to the binding constant of soluble proteins without membrane anchors. Because the binding constant of soluble proteins is readily accessible in experiments, our results provide a useful route to compute the binding constant of membrane-anchored receptor and ligand proteins. A central problem in cell adhesion is to quantify the binding affinity of the membrane-anchored receptor and ligand proteins that cause adhesion (1-4). The distinction of "self" and "foreign" in cell-mediated immune responses, for example, depends on subtle affinity differences between receptor and ligand proteins anchored on the surfaces of apposing cells (5). The binding affinity of anchored receptor and ligand proteins, which are restricted to the two-dimensional (2D) membrane environment, is typically described by the binding equilibrium constant K 2D of the proteins. Because K 2D is difficult to measure in experiments, it is often estimated from the binding constant K 3D of soluble variants of the receptors and ligands that lack the membrane anchors and are free to diffuse in three dimensions (3D). Standard approaches are based on the relation K 2D = K 3D =l c suggested by Bell et al. (6), where l c is a characteristic length that reflects the different units of area and volume for K 2D and K 3D , respectively. However, different methods to measure the binding equilibrium constant of membraneanchored proteins have led to values of K 2D and associated values of l c that differ by several orders of magnitude (7). In contrast to the standard approaches, the simulation data and theory presented here indicate that the relation between K 2D and K 3D involves three different length scales, and that the most important of these length scales is the membrane roughness resulting from shape fluctuations on nanoscales. Because the membrane roughness depends on the concentration of the receptor-ligand bonds that constrain the shape fluctuations, our results help to understand differences in K 2D values from different experiments.In this article, we report simulations of biomembrane adhesion with a molecular model of lipids and proteins (Fig. 1A). We systematically vary the size of the membranes and the numbers of receptors and ligands and determine...

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Binding cooperativity of membrane adhesion receptors

Cited by 76 publications

References 50 publications

Model for Probing Membrane-Cortex Adhesion by Micropipette Aspiration and Fluctuation Spectroscopy

Model for Probing Membrane-Cortex Adhesion by Micropipette Aspiration and Fluctuation Spectroscopy

Inter-membrane adhesion mediated by mobile linkers: Effect of receptor shortage

Binding constants of membrane-anchored receptors and ligands depend strongly on the nanoscale roughness of membranes

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