How Do You Count Individual Biological Bonds

Todd Sulchek Staff ScientistBiosecurity and Nanosciences LaboratoryLawrence Livermore National Laboratory My research program focuses on the measurement and prediction of how multiple individual biological bonds produce a coordinated function within molecular and cellular systems. In particular I focus on two complementary goals. The first is to understand the kinetics of multivalent pharmaceuticals during their targeting of disease markers. The second is to quantify the host cell signal transduction resulting from pathogen invasion. We develop and employ several tools to accomplish these goals. The primary platform for study is the atomic force microscope (AFM), which controls the 3D positioning of biologically functionalized micro- and nanoscale mechanical probes. This talk will describe our method of using single molecule dynamic force spectroscopy to determine the binding strength of antibody- protein complexes as a function of binding valency in a direct and simple measurement. We used the atomic force microscope to measure the force required to rupture a single complex formed by the MUC1 protein, a cancer indicator, and therapeutic antibodies that target MUC1. We will show that nanomechanical polymer tethers can be used in a completely novel manner to count the number of biological bonds formed. Mechanical work (on the scale of a few kBT!) will disrupt these bonds and can quantify the overall kinetics. This ability to form, count and dissociate biological bonds with nanomechanical forces provides a powerful method to study the physical laws governing the interactions of the biological molecules.

Location: Troyland Apartments (TAP) - er Hall of Humanities, (THH) Rm 116

Audiences: Everyone Is Invited

Contact: April Mundy