Adhesion forces measured between a calcium blocker drug and its receptor in living cells using atomic force microscope

Abstract

The adhesion force between the tip of an atomic force microscope cantilever derivatized with nimodipine (a calcium blocker, from the dihydropyridine class, currently used in clinical medicine for hypertension) and living cells of Saccharomyces cerevisiae (unicellular eukaryotes which portray ultrastructural features characteristic of higher eukaryotic cells) was measured. This methodology allowed us to locate (and visualize) pores on the cell surface which may be responsible for calcium transportation in the living cells. The interaction of the cantilever derivatized with the calcium blocker and a pore, which can be a calcium channel, is more intense than a nonderivatized cantilever and the pore. Outside the pore (on the rest of cell surface), a derivatized or a non-derivatized cantilever has the same pattern of adhesion force. The information obtained with this method is very important for the design of new, more potent and less toxic drugs for pharmacological use. ß

The initial single yeast cell adhesion on glass via optical trapping and Derjaguin–Landau–Verwey–Overbeek predictions

“…It is admitted that yeasts exchange this divalent cation outward. 6,10,13 However, Ahimou et al 44 concluded that the electrostatic surface distribution is heterogeneous for pH less than 6, corresponding to this study. Considering their results and AFM accuracy, this conclusion is carefully written but can be discussed at the nanometer length scales.…”

“…Indeed, the yeasts are provided with ion channels allowing solute transport and notably Ca 2+ . 6,10,13 Divalent cation in the suspending medium can have considerable effect. By adding 3 mM of calcium in a 100 mM NaCl solution, the local counterion concentration of a negative-charged surface equals 5M of Na + and 7M of Ca 2+ .…”

“…12 Moreover, ionic transfer between the yeasts and the extracellular medium via channels is now well understood. 6,10,13 To probe the relevant scales affecting the mechanisms of yeast adhesion, an optical tweezer device was set up. The time-dependent mechanisms on glass substrates were ob-served and interpreted in terms of interaction forces of the yeast/glass system and through Derjaguin-Landau-Verwey-Overbeek ͑DLVO͒ and extended DLVO ͑XDLVO͒ calculations.…”