Project Overview

NIRT: Ligand Nanodisplay for Cellular Internalization and Super-Activation

# 0609000
Prabhas Moghe (Principal Investigator)
Thomas Tsakalakos (Co-Principal Investigator)
Jean Schwarzbauer (Co-Principal Investigator)
David Talaga (Co-Principal Investigator)
Charles Roth (Co-Principal Investigator)

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 cell activation; 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.

This research can help design improved nanomaterials for potential cell targeting applications in wound healing, tissue engineering, drug delivery, and cancer therapy. The nanoparticles designed here are biodegradable, can be targeted to cells, and can be customized to cell functions by altering their size. 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 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.

Source: NSF