The adhesion between a microvillus-bearing cell and a ligand-coated substrate: a Monte Carlo study

In biology, specific cell adhesion is mediated by receptor-ligand interactions. Consequently, its strength correlates with the strength of single receptor-ligand bonds that can be measured with a variety of techniques. However, whether single receptor-ligand bonds are truly present in an experiment is often a concern. In this paper, we present a Monte Carlo simulation of the adhesion between a microvillus-bearing cell and a ligand-coated substrate. In the simulation, ligands were immobilized on the substrate either uniformly or in clusters of three and seven, while receptors were distributed uniformly on the microvillus tip and they moved randomly on the cellular surface. How ligand clustering affects the adhesion frequency and forward rate constant was studied. Other factors that were studied include receptor aggregation on the microvillus tip, ligand density, receptor density, contact time, and binding pocket size. In the case of uniformly distributed ligands, our simulation results agree well with those obtained from probabilistic analysis. We found that, even with clustered ligands on the substrate, most of the adhesion events were mediated by a single bond if the total adhesion frequency was less than 20%. Besides, ligand clustering decreased the total adhesion frequency and forward rate constant, but increased the single-bond adhesion frequency under comparable conditions. These findings should lend us some assistance in identifying single bonds in cell-substrate or cell-bead adhesion measurements and in illustrating some biological mechanisms that involve clustered ligands.