NIRT: Creating Functional Nano-Environments by Controlled Self-Assembly

Project Information

Principal Investigator	Matthew Tirrell
Institution	University of California-Santa Barbara
Project URL	View
Relevance to Implications	Marginal
Class of Nanomaterial	Engineered Nanomaterials
Impact Sector	Human Health
Broad Research Categories	Hazard Response Characterization
NNI identifier

Funding Information

Country	USA
Anticipated Total Funding	$1,600,000.00
Annual Funding	$320,000.00
Funding Source	NSF
Funding Mechanism	Extramural
Funding Sector	Government
Start Year	2001
Anticipated End Year	2006

Abstract/Summary

The work proposed here aims to develop the science of spontaneously dividing three-dimensional space into compartments, that is, into controlled environments, at the nanometer size scale, in order to accomplish several engineering objectives. The objectives include: controlled release of therapeutic agents (e.g., drugs, genetic materials); controlled access to biofunctional components (switching or masking activities when desirable); embedding biological signaling within 3D matrices (nano-phase-separated block co-polypeptides decorated with targeting or “homing” ligands) and using surface patterning and templating to produce novel or tailored structures and environments. Four project areas encompass and organize our overall plan: 1. Creating nano-environments via lipid encapsulation; 2. Nano-environments from peptide amphiphiles; 3. Amphiphilic block copolypeptides with hierarchical structures; 4. Patterned surfaces for self-assembly. The work we will do is conceptually similar to creating artificial cells in the sense of separating regions for different functions (without any attempt to build in self-replication). We are aiming toward bio-mimetic structures for functions that may not be naturally occurring, and that mimic or supply interesting functionality. The kinds of functions we wish to incorporate vary from biological (e.g., cell adhesion) to non-biological (e.g., fluid connectivity). The science we will pursue is the principle of spontaneously creating compartments or confined regions with a definite inside and outside. As a practical matter, this means delving deeper into controlled formation of micelles, vesicles, domains, tubules and other controlled regions, as part of larger assemblies of nanoscale components. We will synthesize new lipid-like and macromolecular architectures to drive self-assembly in ways that can encapsulate some species and exclude or display others, controllably, on the interiors and exteriors, respectively, of defined regions. Our research will produce new materials for biomedical applications, new therapeutic approaches based on controllable binding and transport processes and new ways of integrating biological structures with semiconductor fabricated devices. Our core expertise includes extensive experience with lipid and macromolecular structure and phase behavior, based on substantial ability to synthesize new molecules. We have experience with assessing and influencing biological activities and functions, ranging from cell adhesion, to drug delivery and gene transfection, to the roles of metal ions in growth processes and pathological conditions. Characterization expertise and facilities for all of this work are readily available among the members of this collaboration: electron microscopy (adapted in several ways for soft, wet, biological samples), scanning probe nicroscopies, optical microscopy (with fluorescence, confocal, interference and video capabilities), surface force measurements, x-ray and neutron scattering, neutron reflectometry and organic synthesis. The interdisciplinary talents of this team are essential to educate students broadly in the new fields of nanotechnology and biotechnology. The five graduate students and one postdoctoral fellow supported by this proposed grant will work in broad areas of the overall project where interests of several groups overlap strongly. In this way, the students will have continued exposure to the full interdisciplinary group of biochemists, chemists, physicists, chemical engineers and materials scientists that make up our team. An active effort is planned to attract a diverse population of students to this project. We believe that the students and fellow trained in the course of this research will be extraordinarily flexible in their talents, and therefore exceptionally, well-prepared for careers in industry or universities, because of the multiple advisor, multiple technique environment we will provide. The PI and co-PI’s will manage this project to continuously promote this interdisciplinary approach in the selection of specific projects to be pursued. The efforts from this project will feed new ideas, examples and practical experience into a new laboratory-based course under development entitled, “Biomaterials Preparation and Characterization”.