Molecular accessibility in relation to cell surface topography and compression against a flat substrate.

The recruitment of cells to the vascular wall in vivo or the capture of cell subpopulations at the surface of a fabricated device requires the formation of bonds between specific molecular pairs on the cell and the substrate. The ability of a molecule to form a bond depends critically on its localization relative to the cell surface topography. In this report, we present a framework for the quantitative assessment of molecular availability that accounts for the deformability of the cell surface and the balance of forces in the interface, as well as the variability of surface protrusion lengths and the preference for molecules to reside at or away from the tips of surface projections. We also examined how molecular availability should change with increasing compression of the cell against the substrate. Finally, we convolved the distribution of molecules at the interface with a decaying evanescent excitation to predict the fluorescence intensity in total internal reflectance fluorescence microscopy, which can provide a quantitative measure of the relative availability of different molecules at a cell-substrate interface. Model predictions show good agreement with measurements of fluorescence intensity of different molecules labeled fluorescently on the surface of a human neutrophil compressed against a glass surface.