Proteins have many structural and mechanical roles in the body from collagen in bones to titin in muscles and from integrin on the cell surface to ion channels within cell membranes. Recently, it has been shown that special Atomic Force Microscopes, """"""""pullers,"""""""" can be used to measure the mechanical properties of individual molecules by pulling on them. The force vs. distance curves from these pullers contain information about bonds within molecules and about bonds between molecules. This information could lead to a deeper understanding of pathologies associated with the structural and mechanical properties of proteins and give insight into possible remedies. There are, however, problems with the existing pullers that are available for general use. As examples: 1) the force noise in the pullers currently used for this work is significantly larger than it needs to be, obscuring subtle features due to weak bonds. 2) Existing pullers do not combine the Atomic Force Microscope's imaging abilities for selecting molecules together with accurate sensors to measure the distance of pulling. Other problems are detailed in the body of the proposal. Work is proposed here to improve the instruments that are available for general use by three stages of instrument development: (1) adding small cantilever capability for increased force resolution (a factor of 5) and increased speed (a factor of 30) while retaining accurate position measurement and imaging, (2) adding optical access for microscope objectives with high numerical aperture and (3) moving only the cantilever in both pulling and imaging to avoid high frequency shaking of delicate samples like cell cultures.
| Lescun, Timothy B; Hoffseth, Kevin; Yang, Henry T et al. (2016) Effect of various testing conditions on results for a handheld reference point indentation instrument in horses. Am J Vet Res 77:39-49 |
| Drake, Barney; Randall, Connor; Bridges, Daniel et al. (2014) A new ion sensing deep atomic force microscope. Rev Sci Instrum 85:083706 |
| Farr, Joshua N; Drake, Matthew T; Amin, Shreyasee et al. (2014) In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res 29:787-95 |
| Szabo, M E; Thurner, P J (2013) Anisotropy of bovine cortical bone tissue damage properties. J Biomech 46:2-6 |
| Randall, Connor; Bridges, Daniel; Guerri, Roberto et al. (2013) Applications of a New Handheld Reference Point Indentation Instrument Measuring Bone Material Strength. J Med Device 7:410051-410056 |
| Guerri-Fernandez, Roberto C; Nogues, Xavier; Quesada Gomez, Jose M et al. (2013) Microindentation for in vivo measurement of bone tissue material properties in atypical femoral fracture patients and controls. J Bone Miner Res 28:162-8 |
| Barnard, H; Drake, B; Randall, C et al. (2013) Deep atomic force microscopy. Rev Sci Instrum 84:123701 |
| Bridges, Daniel; Randall, Connor; Hansma, Paul K (2012) A new device for performing reference point indentation without a reference probe. Rev Sci Instrum 83:044301 |
| Barnard, H; Randall, C; Bridges, D et al. (2012) The long range voice coil atomic force microscope. Rev Sci Instrum 83:023705 |
| Szabó, M E; Zekonyte, J; Katsamenis, O L et al. (2011) Similar damage initiation but different failure behavior in trabecular and cortical bone tissue. J Mech Behav Biomed Mater 4:1787-96 |
Showing the most recent 10 out of 45 publications
