Receptor-mediated cell attachment and detachment kinetics. I. Probabilistic model and analysis

Abstract

The kinetics of receptor-mediated cell adhesion to a ligand-coated surface play a key role in many physiological and biotechnology-related processes. We present a probabilistic model of receptor-ligand bond formation between a cell and surface to describe the probability of adhesion in a fluid shear field. Our model extends the deterministic model of Hammer and Lauffenburger (Hammer, D.A., and D.A. Lauffenburger. 1987. Biophys. J. 52:475-487) to a probabilistic framework, in which we calculate the probability that a certain number of bonds between a cell and surface exists at any given time. The probabilistic framework is used to account for deviations from ideal, deterministic behavior, inherent in chemical reactions involving relatively small numbers of reacting molecules. Two situations are investigated: first, cell attachment in the absence of fluid stress; and, second, cell detachment in the presence of fluid stress. In the attachment case, we examine the expected variance in bond formation as a function of attachment time; this also provides an initial condition for the detachment case. Focusing then on detachment, we predict transient behavior as a function of key system parameters, such as the distractive fluid force, the receptor-ligand bond affinity and rate constants, and the receptor and ligand densities. We compare the predictions of the probabilistic model with those of a deterministic model, and show how a deterministic approach can yield some inaccurate results; e.g., it cannot account for temporally continuous cell attach mentor detachment, it can underestimate the time needed for cell attachment, it can overestimate the time required for cell detachment for a given level of force, and it can overestimate the force necessary for cell detachment.

BCR-ABL–induced adhesion defects are tyrosine kinase–independent

“…Due to the unique geometry of the detachment device, we assay a range of shear stresses during each spin and observe changes in adhesion throughout the entire range of forces that are tested. The cell detachment device generates a range of detachment forces (0-100 dyne/cm 2 ) on a single fibronectin-coated coverslip, allowing our data to be fitted to known models of cell adhesion, 16,17,29,30,38 and recapitulates shear stresses commonly found throughout the human body. It should be noted that the precise hydrodynamic environment of the bone marrow is unknown; however, it is likely that some of the forces generated by the detachment device exceed forces found in the bone marrow.…”

“…The critical shear stress, 50 , (ie, adhesion strength) is the force required to dislodge half of the cells and is a measurement of the strength of association between cells and fibronectin. 29,30 The 50 is averaged for a set of identical experiments and can be compared over different conditions, such as with and without P210 BCR-ABL expression ( Figure 2B). Expression of P210 BCR-ABL led to an increase in the average critical shear stress, 50 , from 35.1 dyne/cm 2 to 59.6 dyne/cm 2 , indicating that adhesion increased approximately 1.7-fold.…”

“…The convective fluid flow that is established by a spinning disk has been characterized, 27,28 and the fraction of beads or cells under shear flow that remain bound to an adhesive surface is known to follow a sigmoid-shaped profile. 17,29,30 Adhesion profiles for this study were prepared 16 and were accepted for R 2 Ն 0.80, with the exception of runs using matrices consisting of BSA alone or when Meg-01 cells were treated with the RGD peptide due to the few cells that remain attached in the absence of fibronectin. The critical shear stress, 50 , was measured as the surface shear stress, , at an adherent fraction of 0.50.…”

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

“…The appearance of behavioral discontinuity and randomness is strongly suggestive that these adhesions were mediated by a few bonds. 12 It seems logical to reason that the progression of such discontinuous and random behavior, as the binding sites are further diluted, may lead to single-bond conditions. The question is: is it always the case?…”

Murine Sperm-Zona Binding, A Fucosyl Residue Is Required for a High Affinity Sperm-binding Ligand

“…Results from the competitive sperm-ZP binding assay are described by the probabilistic model of cell binding of Cozen-Roberts et al (23). This model predicts that the probability that a sperm will bind a ZP-enclosed egg is a function of the incubation time of sperm with eggs, the number of unoccupied receptors on the sperm, and the rates of association and dissociation of sperm surface binding sites from specific ligands.…”