Professor of Physics, University of Massachusetts
Ph.D.: University of California at Santa Barbara
Single Molecule Biophysics
We use and develop tools for measuring and manipulating single molecules. Our goal is a better understanding of how biological molecules and molecular complexes behave in confining and complex environments, up to and including living cells. Using physical principles and optical tools, our research is motivated by a desire to understand how individual biomolecular components work together to drive the behavior of living systems.
We often make use of high-quantum-yield fluorophores (dye molecules), which are attached to the biomolecule under study. These bright fluorophores act as nanoscopic probes of their local environment, their brightness and spectrum reporting, for example, on changes in biomolecular structure or dynamics.
It is remarkable that individual molecules can be probed at all, but today it is possible to "see" single molecules with electron, optical, and atomic force microscopies, and to pull on and measure the force exerted by individual molecules using microfabricated cantilevers or optical tweezers. Indeed, single-molecule-sensitive measurements have become ubiquitous since the turn of the millennium, and the exquisite sensitivity they offer is providing valuable new insights into biological and biophysical processes.
Currently there are two classes of systems under study in our lab.
Nucleic Acids. We study the conformational dynamics of small DNA and RNA molecules, in an effort to understand structural changes that are transient, irreversible, or stochastic in nature.
Cellulose is the most abundant polymer on earth, but very little is understood about how plants make it. In collaboration with Tobias Baskin, we study the nanomechanics of cellulose and cellulose synthesis in land plants.
One unique aspect of our in vitro work is the use of nanoscopic emulsion droplets for confining individual molecules. Observing an individual molecule for more than a few milliseconds requires a method to locate and hold the molecule in a detection region. Often this is done by attaching the molecule to a surface, or embedding it in a gel. We use reverse emulsion droplets - smaller than a micron in diameter - as nanoscopic "test tubes" for measurements on single molecules.
B.D. Gamari, D. Zhang, R.E. Buckman, P. Milas, J.S. Denker, H. Chen, H. Li, L.S. Goldner. Inexpensive Electronics and Software for Photon Statistics and Correlation SpectroscopyAmerican Journal of Physics To be published (2013).
P. Milas, B.D. Gamari, L. Parrot, B.P. Krueger, S. Rahmanseresht, J. Moore, L.S. Goldner. Indocyanine Dyes Approach Free Rotation at the 3′ Terminus of A-RNA: A Comparison with the 5' Terminus and Consequences for Fluorescence Resonance Energy Transfer. J. Phys. Chem. B, 117(29), 8649-8658 (2013).
L.S. Goldner, A.M. Jofre, J. Tang. Droplet Confinement and Fluorescence Measurement of Single Molecules Methods in Enzymology 472, 61-88 (2010).
J. Tang, A.M. Jofre, R.B. Kishore, J.E. Reiner, K. Helmerson, M.E. Greene, G.M. Lowman, J.S. Denker, C.C.C. Willis, K. Helmerson, and L.S. Goldner. Generation and Mixing of Subfemtoliter Aqueous Droplets on Demand. Analytical Chemistry 81, 8041-8047 (2009).
J. Tang, A.M. Jofre, G.M. Lowman, R.B. Kishore, J.E. Reiner, K. Helmerson, L.S. Goldner, and M.E. Greene. Green Fluorescent Protein in Inertially Injected Aqueous Nanodroplets. Langmuir 24, 4975-4978 (2008).
A.M. Jofre, J. Tang, M.E. Greene, G. M. Lowman, N. Hodas, R. Kishore, K. Helmerson, and L.S. Goldner. Hydrosomes: Femtoliter Containers for Fluorescence Spectroscopy Studies. Proceedings of SPIE 6644 (2007).
Zheng, H., Goldner, L.S. and Leuba, S.H. Homebuilt single-molecule scanning confocal fluorescence microscope studies of single DNA/protein interactions. Methods 41(3), 342 (2007).
D. Kim, K. Okamoto, L.S. Goldner, and J. Hwang. Characterization of single functionalized quantum dots using combined atomic force and confocal fluorescence microscopy. Proceedings of SPIE 6096, 60960G-3 (2006).
J.E. Reiner, A.M. Crawford, R.B. Kishore, L.S. Goldner, K. Helmerson, and M.K. Gilson. Optically trapped aqueous droplets for single molecule studies. Appl. Phys. Lett. 89, 013904 (2006).
P.B. Yim, X. Zhang, E.S. DeJong, J.M. Carroll, J.P. Marino and L.S. Goldner. Single RNA kissing complexes studied by fluorescence resonance energy transfer. Procedings of SPIE 5699, "Imaging, Manipulation, and Analysis of Biomolecules and Cells: Fundamentals and Applications III, D.V. Nicolau, J. Enderlein, R.C. Leif , D.L. Farkas and R. Raghavachari, Eds. 450-460 (2005).
L.S. Goldner, M.J. Fasolka and S.N. Goldie. Measurement of the local diattenuation and retardance of thin polymer films using near-field polarimetry . (preprint) in "Applications of scanned probe microscopy to polymers,"J.D. Batteas, C.A. Michaels and G.C. Walker, Eds. ACS Symposium series 897 (2005).