| The involvement of proteins/peptides in numerous biological processes including signaling, catalysis, ion coordination, active transport, and structural support have made these naturally occurring molecules worthy templates for the design of functional, synthetic materials. This functionality arises from the initial sequencing of monomeric, amino acid subunits and the subsequent folding of these residues into higher order structures. In many cases however, overall functionality results from the interactions at localized "active sites" within the molecule. For this reason, the design of smaller "biomimetic" peptides is advantageous in that functionality may be preserved while eliminating any unnecessary complexity associated with tertiary/quaternary structuring. This thesis work aims to understand fundamental primary sequence-secondary structure relationships of model peptides and then examine the influence of this behavior in two specific applications, microbubbles for imaging and liquid crystals for detection.;In the first section of this work, we discuss the design and synthesis of the two model peptide molecules that serve as the primary focus of our studies. We present two rationally designed molecules of equal chain length with the lone difference being the distribution of charged residues along the peptide backbone. First, we investigate the influence of charge spacing on secondary structure by performing circular dichroism measurements and secondary structure best-fit analysis. Additionally, we program our sequences to display surface-activity upon folding and demonstrate this behavior through Wilhelmy plate surface tension measurements.;In the next section, we examine the incorporation of our model molecules into the monolayer surface of lipid-based microbubbles for the development of "theranostic" assemblies. We first investigate the impact that peptide binding has on the size populations and peptide secondary structure of both precursor and microbubble suspensions. Next, experiments to quantify bound peptide concentrations on the surface are conducted to examine the role of formulation composition. Furthermore, we apply these findings to ultrasound experiments, determining the acoustic properties of our microbubbles as a function of peptide structure at the interface and demonstrate a structural dependence on dissolution kinetics. Lastly, we describe an in vivo application of microbubbles to reversibly, increase the transport of large molecular weight molecules across the blood-brain barrier for enhanced drug delivery.;In the final section, we discuss the development of an optical configuration to measure the dynamics of adsorption of our model molecules to an aqueous/liquid-crystal interface. We demonstrate the use of this simple setup to optically monitor the role of charge distribution on adsorption and obtain quantitative information about the process. Our results suggest both model peptides follow a diffusion-limited adsorption model and these findings show a charge distribution dependence on adsorption rates. Finally, we discuss the implications of these findings for the evolution of our system as a transduction method for specific-binding interactions. |
