This project explores the mechanical properties of enzymes, which are, with DNA, the molecules most central to life. Enzymes operate like nano-scale machines complete with moving parts, yet the mechanics of the large molecular deformations they undergo is hardly characterized. The project addresses this knowledge gap. It is based on a unique experimental technique which is revealing unsuspected materials properties of these large but compact molecules. It turns out that enzymes are mechanically similar to 'silly putty' ! By characterizing the surprising materials properties of the molecules of life, the small team, comprising the PI and two graduate students, expands basic knowledge of molecular scale phenomena in a fundamental direction. On the educational side, the graduate students involved in the project acquire a unique perspective and rare, truly interdisciplinary technical skills. They think like physicists, and at the same time are technically competent with the molecular biology techniques necessary to lead the development of a new materials science of biomolecules.
Enzymes are deformable molecules, but what is the dynamics of this remarkable 'softness' ? Armed with a unique experimental tool which allows, for the first time, sub-Angstrom resolution measurements of enzyme deformability, the small research team (comprising the PI and two graduate students) is discovering surprising yet fundamental materials properties of these compact macromolecules. This project aims to characterize the recently discovered viscoelastic mechanical response of the folded enzyme, its physical origin and generality. The proposed measurements specifically address the temperature dependence of the internal dissipation for conformational motion, as well as the origin (surface effect / bulk effect) of this dissipation. The broader goal of the proposed experiments is to develop a continuum mechanics approach to the study of conformational motion. This approach may uncover universal features of the mechanics of enzymes, which are not apparent in the traditional kinetic description. One example is the viscoelastic transition; more generally, these experiments impact our understanding of dissipative dynamics in molecular scale systems. Finally, the PI's aim is to build an understanding of what is general and what is system specific in the mechanics of enzymes and biomolecules generally. This knowledge is essential for the design of modular, artificial molecular control systems. The experimental method ('nanorheology'), invented in the PI's lab, measures the ensemble averaged deformation of the folded state of a protein elicited by an applied oscillatory stress. The technique measures the mechanical susceptibility of the sample molecule in the relevant frequency range (10 Hz - 10 kHz) and for deformations in the relevant sub-Angstrom to sub-nanometer regime.