The aim of this proposal is to develop and implement a novel instrument designed to measure forces and displacements at the nanoscale level. The instrument can fill the void between molecular-scale capability of optical tweezers and the large-scale force capability of common commercially available transducers. The new approach is based on deflection of a miniature cantilever, manufactured by cutting-edge nanofabrication methods. The levers have undergone preliminary design and development to work out the inevitable """"""""bugs"""""""" and are now ripe for final development and testing. For such tests, the most natural specimens are those that generate force and motion; thus, the investigators will employ both muscle and several other motile specimens such as kinesin and tubulin. As the instrumentation is tested on these specimens, it may be possible to answer fundamental questions that bear on the force-generating mechanism. If the experimental tests are successful, the instrumentation will have proved itself in a demanding setting and should prove attractive for use in a wide range of biological systems in which force ranges from pN up to mN are of interest. Examples (among many) include measurements of phospholipid-membrane stiffness, flagellar and ciliary bending forces, streaming pressure, acrosomal extension force, stereociliary bending force, mechanoreception, etc. The levers can be custom designed for the particular application, they are cheap to produce, and they require a minimum of inexpensive off-the-shelf instrumentation to make functional. Like the optical trap, the investigators anticipate they could become a common commodity among cell biologists and biophysicists.
