"Development of high force optical trapping methods to study complex biological systems"

Optical traps allow the precise application of forces to soft and biological materials. A large number of biophysics applications, including most single-molecule measurements of motor proteins and biopolymers, require forces in the range of one to a few tens of picoNewtons (pN) of force, which is easily achieved using a standard single-beam gradient optical trap. However, higher forces are often desired, for example to study collective behavior of multiple motor proteins, to activate mechanotransduction pathways in cells, or to probe the viscoelastic properties of cytoskeletal networks and other stiff polymeric materials. In principle, it is possible to increase force by increasing the laser power, objective lens numerical aperture, or index of refraction of the trapped object. In practice, even after these inputs are optimized, the application of forces >100 pN remains challenging. Here, I will discuss my laboratory's recent work on an improved method for calibrating the nonlinear region of a single-beam gradient optical trap which substantially increases the maximum force that can be reliably applied. Through an analysis of the position fluctuations of a trapped object that is displaced from the trap center by controlled flow we measure the local trap stiffness in both the linear and nonlinear regimes without knowledge of the magnitude of the applied external forces. This approach requires only knowledge of the system temperature, and is especially useful for measurements involving trapped objects of unknown size, or objects in a fluid of unknown viscosity. Applications of this technique to biological problems will also be discussed.

Megan T. Valentine received her B.S from Lehigh University ('97), M.S. from UPenn ('99) and Ph.D. from Harvard ('03), all in Physics. She completed a postdoctoral fellowship at Stanford in the Department of Biological Sciences, where she was the recipient of a Damon Runyon Cancer Research Postdoctoral Fellowship, and a Burroughs Wellcome Career Award at the Scientific Interface. In 2008, she joined the faculty at the University of California, Santa Barbara, where she is now an Associate Professor of Mechanical Engineering. Her interdisciplinary research group investigates many aspects of biophysics and biomechanics, from regulation of intracellular transport, to shape control of cell division, to design of novel bioadhesives. In 2013, she was awarded an NSF CAREER Award for her work on neuron mechanics, and in 2015 was awarded a Fulbright Award to study adhesion mechanics in Paris, France. She is an Associate Director of the California NanoSystems Institute, and a co-leader of an IRG on Bio-inspired Wet Adhesion within the UCSB Materials Research Laboratory, an NSF MRSEC.