In addition to its annual lectures, ChBE hosts a weekly seminar throughout the year with invited lecturers who are prominent in their fields. This seminar will be held on Wednesday, Dec. 11, in the Ford ES&T Building, Room L1125, at 3 p.m. 

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Interfacial Heterogeneity of Proteins at the Molecular Level

Interfaces are encountered in many experimental systems that alter the behavior of molecular adsorbates relative to bulk solution. For example, stable proteins in solution commonly aggregate and form films at interfaces that can inhibit industrial separations or long-term storage of drug products, alter the wear resistance of artificial joint surfaces, or mediate cellular responses to regenerative tissue scaffolds. Thus, there is intense interest in understanding exactly how interfacial properties influence molecular behavior. Common techniques for probing interfacial phenomena measure the average surface coverage, mobility (i.e. diffusion), molecular conformation, and macroscopic behavior (e.g. anti-adhesive qualities, catalytic activity, etc.). For lack of better information, it is widely assumed that all molecules behave as an average molecule, with a single net adsorption rate, diffusion coefficient, and so on. However, in many systems, important behavior stems from molecules that deviate significantly from the norm. 

This work addresses interfacial heterogeneity at the molecular level in a variety of different proteins that dynamically explore chemically modified glass surfaces. Single-molecule resolution, provided by total internal reflection fluorescence microscopy, allows independent, simultaneously occurring behaviors to be characterized separately. We have previously observed that, while direct attractions between proteins and surfaces are relatively weak, clusters of proteins exhibit surface residence times that increase exponentially with the number of constituents. This work will present several new observations in this area, including: direct measurements of cluster formation dynamics, surface-induced conformational changes, and the effect of surface-induced denaturation on the binding of fibronectin domains to model cell adhesion receptors. In total, these observations lead to a deeper understanding of interfacial phenomena than can be discerned from the average behavior.