Adhesion forces measured between a calcium blocker drug and its receptor in living cells using atomic force microscope.
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 non-derivatized 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.
de Souza Pereira
Ricardo
R
Institute of Biomedical Sciences, Rua Jean Nassif Mokarzel 174, Barão Geraldo, 13084-480 São Paulo, Campinas, Brazil. rsouza@elvispresley.com
da Silva
Maria Ivonete Nogueira
MI
Cotta
Mônica Alonso
MA
D015374:Biosensing Techniques; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D018625:Microscopy, Atomic Force / Q000379:methods*; D009553:Nimodipine / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000648:ultrastructure
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011955:Receptors, Drug; D009553:Nimodipine