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Physics Colloquium – Piotr E. Marszalek
April 19, 2019 @ 3:30 pm - 4:30 pm
Piotr E. Marszalek, Duke University
Nanomechanics of Biopolymers Beyond Their Entropic Elasticity Regime
Compared to other single-molecule techniques, AFM-based force spectroscopy uses stiff force transducers and it may apply large stretching forces to molecules, enabling their structural modifications and capturing high energy conformations that cannot be examined by (for example) X-ray crystallography or NMR. In my talk, I will present our AFM stretching and relaxation studies, supported by computer simulations of individual molecules of DNA and proteins.
While differences between the molecular elasticity of single-stranded and double-stranded DNA were directly determined by optical tweezers as early as 1996, our AFM studies 10 years later captured unexpected similarities between the nanomechanical behavior of single- and double-stranded DNA when they share the same canonical structures, suggesting a common overstretching mechanism. AFM measurements of large multi-domain proteins, combined with coarse-grained Steered Molecular Dynamics simulations, revealed complex unfolding and refolding reactions that do not follow a simple two-state model typically observed for smaller proteins. Taken together, these studies contribute to elucidating the (still not fully understood) mechanism of folding large proteins in vivo and may be useful in examining the mechanism by which large proteins avoid pathways to unproductive and disease-prone misfolded states.