(3j) Dynamic Response of Associating Polymers: From Blood Clotting to Kinetically-Driven Assembly

Recent developments in the fields of supramolecular chemistry and biophysics have demonstrated that there are a rich array of both naturally-occurring and synthetic interactions that rely on complex, long-lived, but ultimately reversible associations. In the case of biological systems, these long-lived associations represent motifs composed of anywhere between one and even hundreds of amino acids depending on the physiological situation; disulfide bonds, integrins, hydrophobic interactions, and any number of more specialized interactions are ubiquitous. I have elucidated the role of such binding behaviors in the specific case of the multimeric protein von Willebrand Factor (vWF), a blood clotting protein that functions as a targeted adhesive at the site of a wounded blood vessel. Despite its complex structure on sub-quaternary levels, the quaternary structure of vWF conveniently lends itself to coarse-grained simulation models that I use to illustrate concepts described through analytical theory. vWF's counterintuitive behavior has remained largely unexplained until my PhD work, which describes how long-lived binding states couple to shear flows to drive an otherwise inert polymer globule into an adsorbed and elongated state despite unfavorable hydrodynamic forces.

Throughout the course of the aforementioned investigation, I developed the simulation and theoretical tools to study polymer systems with long-lived, reversible associations. Due to the coarse-grained nature of these simulations, the principles I have elucidated are largely applicable to designed synthetic systems based on supramolecular chemistry ideas. A host of counterintuitive and kinetically-driven behaviors were observed in the course of understanding single-chain self-associating systems, and it is already clear that these concepts will provide routes to novel, stimuli-responsive, and transient structures. In my future plans, I anticipate using these ideas as the platform upon which I can build designed materials that can form structure in either the bulk or the single-chain limit through these temporal constraints.

My poster will outline the most crucial aspects of my PhD work on von Willebrand Factor, along with an outline of my anticipated projects involving designed, kinetically-driven systems as it relates to both my previous PhD experience and my anticipated Postdoctoral work.