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The maximum receptor-ligand bond spacing to ensure cell adhesion in ligand-coated substrates

Recent experiments by Arnold et al. (ChemPhysChem, vol. 5, 2004, p383 ) revealed that a distance of less than 58-73 nm between receptor-ligand bonds is necessary to ensure focal adhesion in cells adhering to ligand-coated substrate. An elegant solution to this problem is supplied by Lin, Inamdar, and Freund. JMPS, 2008, 56, 242 , J. Mat. Sci. 2007, 42, 8907 . They envision dynamic interactions between cell membranes and substrates as a compliant elastic membrane undergoing thermal undulation; the tendency for receptors in a cell membrane bonding with a ligands in a substrate is represented by an interaction potential. The critical spacing of ligand bonds in their model is the outcome of a competition between thermal motion of the cell membrane and the free energy reduction associated with bonding.

In this paper, we supply a simple dimension analysis to show the dependence of successful focal adhesion growth on the spacing of ligand bonds. Focal adhesion growth  is considered as a process assisted by thermal fluctuations and receptor-ligand binding, and resisted by repulsive “bulge pressure” and membrane deformation. By applying balance between these forces, we obtain  a critical spacing of receptor-ligand bonds. We use typical properties of cell membranes and obtain the critical spacing of receptor-ligand bonds around 39~89nm for a wide range of repulsive “bulge pressure”. Based on the experimental measurement of the critical spacing, we get an estimate for the repulsive “bulge pressure” nearby an adhesion patch during the initiation of focal contact, which is in the order of 1 kPa.

We emphasize that, however, there are both consistency and inconsistency between the experiments and our results. The consistency is that there is a critical spacing between ligand sites to ensure focal adhesion growth. The inconsistency lies in the point of views regarding governing mechanisms for the critical spacing of receptor-ligand bonds. While our analysis indicates that physical forces may actually be the “molecular ruler” that governs receptor-ligand bond distance, Cavalcanti-Adam et al. (Biophys. J. 2007, 92, 2964-2971 ) suggest that such a critical spacing is controlled by biochemical “molecular ruler”. More experiments are certainly desired to identify which “molecular ruler” -- physical, biochemical, or the combination of both --  governs the spacing of receptor-ligand bonds.


The paper
is accepted for publication in Langmuir .

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