NER: Triggering Nanovesicle Functions

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National Science Foundation - Active Nanostructure and Nanosystems (ANN) (NSF 05-610)Nanoscale Exploratory Research (NER)ABSTRACTProposal Number: CTS-0608827 Principal Investigator: Kaplan, DavidAffiliation: Tufts University Proposal Title: NER: Triggering Nanocesicle Functions Intellectual Merit A novel family of biopolymeric amphiphiles (emulsans complex lipoheteropolysaccharides) has been characterized in recent years in which detailed control of structural features (polymer chain length, frequency and chemistry of the lipogenic side chains) can be attained via physiological and genetic manipulation of the biosynthesis. Furthermore, these changes in structure directly impact solution behavior of the polymers, including emulsification and surface tension properties. In recent studies, we have extended these systems to: (a) mimic the native ability of these complex polymers to carry a 'payload' of other molecules (proteins), and (b) form micro and nano-vesicles. The goal of the NER is to develop a fundamental understanding of the control of structure and function of these novel nanovesicle carrier systems and incorporate triggering functions to regulate the release profiles of the payload being carried. To accomplish this goal, we plan to: (1) develop an understanding of the relationships between polymeric amphiphile structure and nanovesicle morphology and stability, and (2) enhance the nanovesicles with actuation functions via enzyme payloads to control the release kinetics of peptides and proteins as payloads from the nanovesicles. The polymer amphilphiles will be formed into nanovasicles with control of structure and morphology based on the specific features of the structural variant, the co-oils used in processing, and the physical process used to form the structures. Detailed structural and morphological characterization will be conducted. Subsequently, a release activating enzyme (lipases with temperature or pH sensitivities to activate/deactivate) will be incorporated into the nanovesicles along with selective model payload compounds (bovine serum albumin, subtilisin enzyme). Lipase enzyme actuation of the nanovesicles will be based on removal of the lipogenic fatty acid side chains of the emulsan, thus negating the interactions with the payload, resulting in release. The activities of the enzyme actuators will be 'triggered' from external factors (pH, temperature). The outcome of this effort will be a fundamental understanding of the relationships between biopolymeric amphilphile structure and function related to passive and active release kinetics of carried molecules. This insight will be critical to future designs of systems to exploit release features, such as for activated surface coatings, controlled release of agriculture and pharmacological contents, self-repairing polymer composites and many related applications.Broader Impact The project will provide fertile ground for interdisciplinary student experiences at both the graduate and undergraduate during one year NER Program. A focus on topics at the intersection between engineering and biology with strong implications in areas of controlled release in drug delivery, surface coatings with activatable functions and many related themes will be stressed. A teaching module will be developed based on the NER program for use in internal courses (undergraduate and graduate level) at Tufts, with input and preparation by the students, as well as for external dissemination via the Center for Engineering Education Outreach are planned as part of the broader dissemination effort for K- 12 education. Technically, the proposed studies have broad implications in areas of environmental, medical and general materials science and engineering systems. For example, the applicability of these systems is potentially broad due to the extensive control of structures and thus functions of this family of biopolymers. In addition the green chemistry used to synthesize the biopolymers and the degradability of the systems upon completion of release functions provides a complete cycle of bio/environmental compatablity. Since the biopolymers are also biocompatible, additional options for utility in vivo can also be considered.