The research objective of this award is to determine the non-equilibrium mechano-chemical behavior of proteins stretched in atomic force microscopes and microfluidic devices. The key novelty of this approach is the use of continuum fluctuating rod models (and allied computational methods) with heterogeneous mechanical properties as representations of partially unfolded proteins rather than fully atomistic descriptions of the biomolecules. The research is divided into three projects: (a) model a globular protein oligomer as a heterogeneous fluctuating rod and determine its response under different loading conditions using a computational technique based on Gaussian integrals, (b) model a coiled-coil protein as a 1D continuum with a multi-well free energy and predict its force-extension response using a theory of phase transitions, (c) understand the kinetics of propagating unfolding fronts in rod-like molecules, such as coiled-coils, using a bead-and-spring model with Langevin dynamics.
If successful this work will have a major impact in unraveling the mechanical behavior of coiled-coil proteins central to the pathogenesis of diseases, such as, muscular dystrophy, premature ageing, stroke, heart disease and wound healing. It will also help understand the response of proteins and DNA under large fluid imposed shears which are encountered in industrial processes in the manufacture of therapeutics. The education plan will impart training to graduate and undergraduate students in the highly interdisciplinary areas of nanotechnology and biophysics by teaching a new graduate course titled Entropic forces in biomechanics and mentoring undergraduates to do short summer projects. The outreach plan includes (a) working with a local start-up company on projects related to mapping the human genome, (b) organizing symposia and advanced schools in international conferences, and (c) activities targeted at minority students and teachers in high schools.