The objective of this proposal is to elucidate the fundamental aspects of selfassembly and pattern formation of well defined sheet forming peptides confined at interfaces. Our approach involves three steps. (1) It is proposed to design and synthesize simple periodic peptide sequences, yielding surface active â-strands that self organize into aggregates to form patterns as a function of the peptide sequence. Rational peptide design allows us to systematically explore the role of hydrophobicity, electrostatics and molecular size on pattern formation. (2) It is proposed to directly address the assembly phenomena using a set of interfacial characterization tools. Multiple length scales can be examined, including molecular length scales, using CD and ATR-FTIR, and at supramolecular length scales, using brewster angle microscopy, fluorescence microscopy and ellipsometry. (3) It is proposed to use two dimensional equations of state that define both the phase behavior and the critical surface concentrations of nascent aggregates at the interface. Subsequently, we can apply these parameters to predict the dimensions of pattern formation.
Broader Impact:
Rationally designed peptides and polypeptides are rapidly becoming useful components in nanostructured materials for applications ranging from drug delivery to energy storage. If successful, the PI's believe that the proposed research will yield fundamental understanding of biomolecular assembly under confinement, and these ideas can be directly applied in hybrid materials design.
CCNY's mission is to provide quality undergraduate and graduate education in a broad range of fields to a highly diverse student body, which is 34% Hispanic, 24% black, 17% Asian and 11% white, classifying our college as a Minority Serving Institution. The PI is dedicated to this mandate that asks for a multiplicity of subject matters to be taught to students of varying backgrounds without sacrificing quality of research or education. In addition to graduate training, undergraduate and high school research support for this work will be coordinated through two mechanisms. (1) NSF has funded NUE, REU and PREM programs at CCNY to provide research experiences for both undergraduate and high school students. (2) The PI has led the CCNY-HSMSE Peer-Learning Program for the last three years. This program provides an opportunity for undergraduates and high school students to engage in engineering and science in the classroom and lab. The PIs have successfully developed this mechanism that allows undergraduate and high school students to explore fundamental engineering and science questions in an engaging setting where peer learning results in common ground to enhance the learning experience.
The goal of this project was to design a new set of biomolecules to explore the fundamentals of protein adsorption and nanoscale surface patterning. A set of amphipathic peptides was designed where we precisely controlled the helicity, surface-activity, and charge distribution of the molecules. Subsequently, we examined the dynamics of adsorption to the air-liquid interface on microbubbles to explore our ability to engineer nanoscale bubbles for ultrasound imaging and drug delivery. Additionally, we examined the dynamics of adsorption to the liquid crystal interface to explore our ability to engineer highly sensitive, robust and inexpensive sensors. The attached figure shows our ability to examine the adsorption of periodically sequenced helical peptides using our surfactant-liquid crystal system. We are currently working to optimize the conditions of this system for the detection of a femtomole of a target biological molecule. Intellectual Merit. Our work advances of the fundamental understanding of the relationship between protein folding and adsorption to interfaces. Our rationally design polypeptides were used to answer basic questions about the nature of biomolecular adsorption, where the dynamics of folding and self-assembly were quantified using precise interfacial tools and a new robust liquid crystal-based tool. We were able to characterize for the first time the role of charge distribution and sequence periodicity on the dynamics of adsorptions, allowing others to quickly examine their own systems for improved interfacial stability and self-life. Moreover, outside our area, our research on curved interfaces has explored the ability of microbubbles to enhance the transient penetration of drug molecules through the blood brain barrier. This new understanding will improve our ability to transport drugs to a previously impermeable organ, allowing us to attack diseases such as brain cancer. Broader Impacts. The broader impacts of our work are two fold. First, we have engineered two new biomolecular systems for the advancement of technologies that benefit society. One system is our peptide-laden microbubbles that push the limits on size for vascular penetration and bubble mechanics for transient penetration of the blood brain barrier. Another system is our liquid crystal platform that pushes the limits on detection sensitivity. Second, we have formed several new high school partnerships in New York City. These partnerships integrate scientists, engineers and educators to engage high school students in the lab and the classroom. Taken together, the technological developments allow us to draw students at all levels who typically do not have opportunities to work in a research environment that fosters engagement and scholarship.
