NSF Award 0609000

Nanoscale Interdisciplinary Research Team (NIRT) Award

Ligand Nanoparticles for Cell Cytointernalization and SuperActivation

Principal Investigator: Prabhas Moghe

Co-PIs: Jean Schwarzbauer, Charles Roth, David Talaga, Thomas Tsakalakos

Abstract:

This proposal was received in response to Nanoscale Science and Engineering initiative, NSF 05-610, category NIRT.  The objectives of this research are (1A) to design, fabricate, and characterize nanoparticles functionalized with matrix protein fragments, and (1B) to elucidate the role of nanoparticle size, ligand sequence and ligand loading on cell motility and matrix assembly; (2) to identify the key molecular signaling pathways that mediate nanoparticle internalization and increased activation of cell motility; and (3) to develop imaging modalities to quantify nanoparticle trafficking and internalization dynamics.  The approach involves the functionalization of albumin-derived nanoparticles with various fragments of fibronectin (ligand).  The first phase of the study will examine how optimal configurations of substrates based on the ligand-nanoparticles can significantly alter the morphology and dynamics (motility, matrix assembly) of skin derived cells (keratinocytes, fibroblasts).  The second phase will focus on identifying the underlying biologic mechanisms using protein and gene level signaling assays.  The third phase will probe the nature and kinetics of nanoparticle-cell interactions using high resolution, two-photon microscopy and a magnetically responsive biosensor platform with nanoscale fidelity.

The nanoparticles designed here are biodegradable, can be targeted to cells, and can be customized to cell functions by altering their size.  For example, smaller nanoparticles can stimulate increased motility in epidermal cells (relevant for skin healing in burns, ulcers) while larger nanoparticles promote skin contractility and matrix assembly (relevant to wound repair).  This research can thus help design improved nanomaterials for cell targeting in wound healing, tissue engineering, drug delivery, and cancer therapy.  This project extends its outreach through the wide diversity network (graduate, postdoc, undergraduate) at Rutgers and beyond, and resonates with three new integrative graduate courses at Rutgers on engineering of cellular biointerfaces with biomaterials, a graduate training program on biointerfaces, and an international research collaboration.

NIRT Faculty:

NIRT Research Group:

Dr. Maria Pia Rossi, Postdoctoral Researcher

Dr. Ram I. Sharma, Postdoctoral Researcher

Christopher Langhammer, Graduate Student in Biomedical Engineering

Vanesa Figueroa-Tanon, Graduate Student in Molecular Biosciences

Jocie Cherry, PhD Candidate in Biomedical Engineering

Xianglan He, PhD Candidate in Chemistry and Chemical Biology

NIRT Collaborators and Partners for Broader Outreach:

Faculty: Joachim Kohn, Kathryn Uhrich

Research Staff and Students: Dominik Naczynski, Lavanya Peddada, Dr. Sadangi, V. Shukla, Charles Florek

Participants: Photograph from Fall 2006 NIRT Meeting

This material is based upon work supported by the National Science Foundation under Grant No.0609000. Any opinions, findings and conclusions or recomendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation (NSF)."