The Aim of this competing renewal is a continued exploration of stepwise sliding of myofilaments. Dynamics of sliding will be explored in two preparations that have been developed in the laboratory of the applicant: a single myofibril preparation in which the dynamics of shortening and lengthening in single sarcomeres is investigated; and, a preparation consisting of a single actin filament sliding over a single myosin or thick filament. Preliminary, evidence in both preparations indicates that sliding occurs in steps and step size is an integer multiple of 2.7 nm (i.e., n x 2.7). Followup experiments are designed to test whether this paradigm is genuine. To this end, control experiments will be carried out on both preparations, and various technical improvements will be implemented to improve resolution. One question is whether lengthening steps and shortening steps show the same stepping paradigm. Another is whether values of n > 1 are artifacts of limited resolution, and whether, with higher resolution, all steps are of a distinct value. Duration of pauses (i.e., periods between steps) will also be explored. The functional dependence of pause duration on load will be explored. Finally, several strategies will be implemented (e.g., diminished overlap of single filament pairs) to reduce the number of cross-bridges to approach one. In such a way, dynamics of sliding with very few cross-bridges will be examined. Although this may not be a """"""""single molecule"""""""" experiment, the advantage is that myosin molecules that interact with actin remain in their natural configuration. Hence, the experiments should yield valuable information on the near-molecular nature of the contractile process. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR044813-06A2
Application #
7099912
Study Section
Special Emphasis Panel (ZRG1-MOSS-E (02))
Program Officer
Nuckolls, Glen H
Project Start
1999-09-30
Project End
2011-02-28
Budget Start
2006-04-01
Budget End
2007-02-28
Support Year
6
Fiscal Year
2006
Total Cost
$427,884
Indirect Cost
Name
University of Washington
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Chai, B; Mahtani, A G; Pollack, G H (2012) UNEXPECTED PRESENCE OF SOLUTE-FREE ZONES AT METAL-WATER INTERFACES. Contemp Mater 3:1-12
Zhao, Qing; Coult, Jason; Pollack, Gerald H (2010) Long-range attraction in aqueous colloidal suspensions. Proc SPIE Int Soc Opt Eng 7376:73761C1-73761C13
Chai, Binghua; Pollack, Gerald H (2010) Solute-free interfacial zones in polar liquids. J Phys Chem B 114:5371-5
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Chai, Binghua; Yoo, Hyok; Pollack, Gerald H (2009) Effect of radiant energy on near-surface water. J Phys Chem B 113:13953-8
Ovchinnikova, Kate; Pollack, Gerald H (2009) Cylindrical phase separation in colloidal suspensions. Phys Rev E Stat Nonlin Soft Matter Phys 79:036117
Zhao, Qing; Ovchinnikova, Kate; Chai, Binghua et al. (2009) Role of proton gradients in the mechanism of osmosis. J Phys Chem B 113:10708-14
Zheng, Jian-ming; Wexler, Adam; Pollack, Gerald H (2009) Effect of buffers on aqueous solute-exclusion zones around ion-exchange resins. J Colloid Interface Sci 332:511-4
Ovchinnikova, Kate; Pollack, Gerald H (2009) Can water store charge? Langmuir 25:542-7
Chai, Bing-hua; Zheng, Jian-ming; Zhao, Qing et al. (2008) Spectroscopic studies of solutes in aqueous solution. J Phys Chem A 112:2242-7

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