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Surface-stress sensors for rapid and ultrasensitive detection of active free drugs in human serum.
- Source :
-
Nature nanotechnology [Nat Nanotechnol] 2014 Mar; Vol. 9 (3), pp. 225-32. Date of Electronic Publication: 2014 Mar 02. - Publication Year :
- 2014
-
Abstract
- There is a 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. Because of the appearance of drug-resistant hospital 'superbugs', there is currently great interest in the destruction of bacteria by bound drug-target complexes that stress 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, Food and Drug Administration-approved drug of last resort, vancomycin, and the 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, that determine dosages in drug therapies. The 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.
- Subjects :
- Anti-Bacterial Agents metabolism
Anti-Bacterial Agents pharmacology
Bacteria drug effects
Bacteria metabolism
Biomechanical Phenomena
Biosensing Techniques instrumentation
Equipment Design
Glycopeptides metabolism
Glycopeptides pharmacology
Humans
Ligands
Lipoglycopeptides
Models, Biological
Solvents metabolism
Surface Properties
Vancomycin metabolism
Vancomycin pharmacology
Anti-Bacterial Agents blood
Glycopeptides blood
Nanotechnology instrumentation
Vancomycin blood
Subjects
Details
- Language :
- English
- ISSN :
- 1748-3395
- Volume :
- 9
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature nanotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 24584276
- Full Text :
- https://doi.org/10.1038/nnano.2014.33