School of Physics Soft Condensed Matter and Biophysics Series: Robert Szoszkiewicz, Kansas State University

Using force spectroscopy mode of Atomic Force Microscopy (AFM) one can measure physiologically relevant pN forces between an AFM tip and a biomolecule with a mean displacement resolution of about 0.1 nm. The last 15 years have witnessed an explosion of interest in single molecule force spectroscopy fueled by: 1) new possibilities to advance in protein folding, 2) possibilities to elucidate molecular mechanisms of various cellular processes, and diseases, and 3) efforts to understand the nanomechanical properties of proteins, polysaccharides and DNAs in order to design biomimetic and/or mechanically functional materials.

In this talk, I will present several examples of our AFM force spectroscopy data. First, I will concentrate on elucidating early folding events in a simple model protein from changes of molecular compliance and dissipation factors. Using such measurements, we hope to provide basic understanding of early folding events. Next, I will show how mechanical force can influence the rate and mechanisms of an enzymatic cleavage of a single disulfide bond embedded in a protein. Time permitting, I will present the results of mechanical unfolding of on a recombinant protein comprising an NRR domain from mammalian Notch 1. Notch is a transmembrane cell signaling protein, and understanding its mechanical properties at the single molecule level is expected to help elucidating Notch’s role in processes relevant to embryonic development, tissue homeostasis, and some breast cancers.