Research in the Webb group seeks to understand and manipulate the mechanisms of interaction, organization, and self-assembly of biological macromolecules that lead to the complex and emergent properties of living systems. We are interested in these topics for two principal reasons. First, understanding the organization of biological systems is of vital biomedical importance. Second, we seek to exploit the weak but long-range interactions involved in noncovalent organization of biological macromolecules at prepared surfaces and interfaces with the ultimate goal of integrating biological and inorganic materials in a controlled and robust manner.

Research in the Webb group is multidisciplinary and employs a variety of physical and analytical techniques. We study the physical chemistry of electrostatic fields at protein-protein interfaces using vibrational spectroscopy coupled with computational methods; we prepare and characterize chemically modified surfaces that interact specifically with folded, functional proteins using X-ray photoelectron spectroscopy, atomic force microscopy, and surface spectroscopic techniques; and we use biochemical control over the dynamic behavior of cytoskeletal fibers tethered to patterned surfaces and monitored through optical microscopy.

Electrostatic Fields at the Protein-Protein Interface

Macromolecular interactions in biological systems are now a major focus of interest. In the post-genomic era, enhanced understanding of the cooperation between biological molecules such as proteins, DNA, RNA, and lipids is necessary to explore the complexity of living cells. Furthermore, molecules that promote or disrupt specific macromolecular interactions have vast pharmacological potential. Macromolecular interactions lead to emergent properties necessary for life, but can only be studied or understood if the molecular-level, noncovalent, electrostatic forces that drive and control those interactions are themselves understood. The Webb group measures electrostatic fields at protein-protein interfaces and seeks to develop computational models that accurately predict these interactions.

Electrostatic Control of Protein Binding at Surfaces

Incorporation of a protein into a sensing, electronic, or biofuel device often requires that the protein be tethered to an inorganic surface. The Webb group uses surface chemical modification to prepare substrates that present an ideal electrostatic interface for the noncovalent binding of proteins in a controlled and organized manner. We are developing surface chemical functionalization techniques that are completely general to allow controlled binding of any protein of interest, including those of unknown structure or complicated molecular biology.

Dynamic Control of Microtubules on Conducting Surfaces

As modern electronic devices have become successively smaller, a pressing need has developed for constructing complex structures from the “bottom up” through the self-assembly of simple building blocks into two-and three-dimensional structures. Biology has many examples of intricate structures that are constructed through the self-assembly of small molecular components. The Webb group studies one such system, the microtubule, which is an exquisitely ordered, three-dimensional structure that is self-assembled through noncovalent, electrostatic interactions of macromolecules. We exploit the biochemical mechanisms of dynamic instability of microtubules that are tethered to a patterned, conducting substrate to generate self-assembled devices that are capable of complex functions such as regulation and feedback.

For further information, please contact Lauren Webb at lwebb@cm.utexas.edu.