Ndieyira, JW; Kappeler, N; Logan, S; Cooper, MA; Abell, C; McKendry, RA; Aeppli, G; (2014) Surface stress sensors for rapid and ultrasensitive detection of active free drugs in human serum. Nature Nanotechnology

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Abstract

There is growing appreciation that mechanical signals can be as important as chemical and electrical signals in biology. To include such signals in a systems biology description for understanding pathobiology and developing therapies, quantitative experiments on how solution phase and surface chemistry together produce biologically relevant mechanical signals are needed. Due to the appearance of drug-resistance hospital “superbugs”, a system of large current interest is the destruction of bacteria by antibiotics forming bound drug/target complexes which stress the bacterial cell membranes. Here we use nanomechanical cantilevers as surface stress sensors together with equilibrium theory to describe quantitatively the mechanical response of a surface receptor to different antibiotics in the presence of competing ligands in solution. The antibiotics examined are the standard, FDA approved drug of last resort, vancomycin, as well as yet-to-be approved oritavancin, which shows promise for controlling vancomycin resistant infections. The work reveals variations among strong and weak competing ligands, such as proteins in human serum, which determine dosages in drug therapies. These findings further enhance our understanding of the biophysical mode of action of the antibiotics and will help develop better treatments, including choice of drugs as well as dosages, against pathogens

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