Physical Society Colloquium

Dynamic Heterogeneity in Single Polymer Relaxation and TALE Protein Dynamics on DNA

Charles Schroeder

Department of Chemical and Biomolecular Engineering
Beckman Institute for Advanced Science and Technology
University of Illinois at Urbana-Champaign

Single molecule techniques provide a powerful method to directly observe the dynamics of polymers and proteins, often revealing surprising behavior and rich heterogeneity at the molecular level. In recent work, my group has extended the study of single polymer dynamics to new polymeric materials such ring-shaped polymers and comb-shaped polymers with complex molecular architectures. In the first part of the talk, I discuss the unexpected observation of dynamic heterogeneity in single polymer motion in entangled solutions. Our results show that two different molecular sub-populations are `hidden' in the ensemble. One sub-population of polymers relaxes via a smooth single-mode decay, whereas a second sub-population relaxes via a two-mode (fast and slow) response. This unexpected behavior is interpreted by considering regions of locally unentangled polymers that arise due to flow-induced `pulling' or disentanglement of polymers in an otherwise well-mixed solution. We further study the dynamics of branched polymers such as comb-shaped polymers using single molecule methods. Our results again reveal unexpected stretching dynamics due to the introduction of branches or side-chains along a long linear polymer backbone. In the second part of the talk, I discuss the DNA target site search mechanism of a class of programmable gene editing proteins called transcription activator-like effector (TALE) proteins. Despite the importance of these proteins for genomic editing applications, little is known about the DNA target site search mechanism. We use single molecule techniques to study the search process for these proteins on long DNA molecules. Our results show that TALEs search DNA like a `molecular zip-line', essentially using moving along DNA without rotating or following the helical pitch of natural DNA. Our results suggest that the intrinsic helical structure of these unique proteins enables them to adopt a loosely wrapped conformation around DNA templates during nonspecific search, facilitating rapid one-dimensional (1D) diffusion under a range of solution conditions. Overall, these results show that the search mechanism for TALE proteins is unique amongst the broad class of sequence-specific DNA-binding proteins.