Executive Summary : | The development of tools like scanning probe microscopy, optical and magnetic tweezers has revolutionized the study of single molecule scale matter. These tools, particularly the Atomic Force Microscope (AFM), measure deflections produced in a micro-cantilever due to stretching a single polypeptide chain. AFM has become an indispensable tool in biophysical measurements, allowing for the analysis of protein folding-refolding dynamics using mechanical perturbation instead of thermodynamic or chemical methods. The field has seen significant activity in recent decades, with a new approach called the small amplitude interferometer-based Atomic Force Microscope. This method measures cantilever displacement, enabling linear measurements, and off-resonance operation to avoid complications from cantilever hydrodynamics. These features are relevant in measuring quantitative viscoelastic response of single molecules in different solvents. This project aims to use the AFM method to measure viscoelasticity of flexible and semi-flextble polymer chains and the viscolelasticity of a single folded state of a protein. The ability to measure internal friction and stiffness of folded structures of biologically relevant heteropolymers has implications for theories of energy landscape and diffusive reactions at the level of single molecules. The project will have a high impact on our understanding of folded states of large single macromolecules from the perspective of condensed matter physics. |