The NSF has awarded a 4-year grant to a Rutgers Nanoscale Interdisciplinary Research Team, or NIRT to study "Ligand Nanodisplay for Cellular Internalization and Super-Activation."
This NIRT proposal has assembled an interdisciplinary team of five principal/co-principal investigators from Rutgers and Princeton; and two supportive collaborators; to elucidate the significance of cellular internalization of nanodisplayed adhesion ligands toward cellular activation and motility. The proposed studies are predicated on a recent discovery by the PI that when traditionally non-internalizable adhesion ligands are displayed from truly nanoscale carriers (<100 nm), the adhesion ligands get endocytosed (internalized), and in the process of this cytointernalization, the ligands trigger greatly increased levels of intracellular biochemical signaling pathways, which leads to superactivation of cell behaviors, including cellular motility that is a major cellular phenomenon for biotechnology and tissue engineering. Because these substrate-based ligand nanocarriers are cleared and internalized by cells upon binding, the interfaces are biodynamic in nature.
The key questions addressed by the NIRT proposal are:
Intellectual Merit: The proposed studies are innovative because they seek to engineer the presentation of well-established protein ligands via nanoscale carriers, in order to superactivate cells in specific ways; and to establish novel biosensing approaches for measurement of nanocarrier cytointernalization. Preliminary studies show that cells triggered to migrate using nanoscale cytointernalizable ligands were significantly more active than the controls, suggesting that nanotechnology can potentially help reveal new signaling domains or expanded signaling capabilities for our current repertoire of biomolecules. The design of a successful nanoscale biointerfacial system will involve the contributions from very diverse scientific professionals, including a cell/matrix biologist (Schwarzbauer) to engineer ligand fragments and examine their intracellular protein-level signaling; a cellular bioengineer (Moghe) to fabricate nanocarriers for the ligand display and quantify cellular function, uptake, and signaling; a molecular bioengineer (Roth) to screen intracellular signaling via parallel DNA microarrays; a physical spectroscopist (Talaga) to evaluate the intracellular trafficking; and inorganic nanomaterials scientist (Tsakalakos) and nanobiosensor expert (Menon) for developing sensors of nanocarrier uptake.
Broader Impact: Insights from the study can potentially impact the development of bioactive nanomaterials for cellular biotechnology; wound healing; tissue regeneration; and molecular biomedicine. The nanoscale platform identified herein can boost cell motility kinetics by an order-of-magnitude, which can reduce the time for wound healing and re-epithelialization, leading to reduced healthcare costs and improved therapies. At Rutgers, the NIRT proposal is particularly timely because it can further foster the growth of cross-disciplinary education and minority outreach in nanotechnology and life-sciences at graduate and undergraduate levels. Using existing partnerships with an existing IGERT program on biointerfaces directed by the PI, the Northeast Alliance for Graduate Education and the Professoriate (NEAGEP), and a tissue engineering postdoctoral training program, the NIRT team will launch a vigorous outreach effort to broaden participation at all levels (graduate, undergraduate, postdoctoral). Through the Rutgers NSF IGERT on biointerfaces (www.igert.rutgers.edu) (one major thrust is micro/nanoscale biointerfaces), the research themes of the NIRT will be disseminated among the undergraduate summer research group of minority students within the RISE (Research in Science and Engineering) program. The NIRT faculty are in various stages of developing three new research-integrative graduate courses, based on the NIRT theme, on cellular/molecular bioengineering; nano- and microsystems biointerfaces; and biointerfacial characterization. These courses will help establish a stronger educational infrastructure for nanoscale science and engineering, which synergizes with three advanced research centers (Keck Collaborative Center; Institute of Advanced Materials; NJ Center for Biomaterials) within New Jersey. The NIRT collaborations will facilitate the offering of an international internship to a NIRT graduate researcher at the Department of Micro/Nanosystems, Technical University, Denmark.
The Nanoscale Interdisciplinary Research Team:
Principal Investigator:
Co-PI's:
Collaborators: