NER: Intracellular Nanoprobes for Physical Manipulation of Cells

Ohio State University Research Foundation -Do Not Use, Columbus OH

Investigators

Abstract

CBET-0707969 Winter The applicant is creating intracellular nanoprobes for the physical manipulation of cells using magnetic nanoparticles (i.e., supraparamagnetic iron oxide nanoparticles (SPIONs)). SPIONs are excellent candidate materials for mechanical cellular nanoprobes because they can serve as physical actuators, producing a controlled, investigator-triggered force in response to a magnetic field. Previously, SPIONs encapsulated in magnetic microspheres have been used to examine the response of cells to extracellular force. These studies demonstrated that the cytoskeleton, a biopolymer network responsible for the mechanical integrity of cells, is part of an elaborate mechanotransduction system that can influence many cell functions. However, these studies use large particles, nearly half the size of a cell, which indirectly interface with the cytoskeleton through extracellular cell surface receptors. Although some attempts have been made to use smaller SPIONs inside a cell, these methods rely on particle endocytosis for delivery. Particles remain trapped in endosomes, unable to interact with cytoplasmic structures. Thus, the potential to manipulate the cytoskeleton directly remains largely untapped. In this proposal the investigator will employ SPIONs as physical intracellular nanoprobes for direct, targeted manipulation of the actin cytoskeleton. As a model system, the role of targeted versus untargeted cytoskeletal manipulation in fibroblast cell migration will be explored. Cell migration is a critical factor in embryonic development, nerve regeneration, tumor metastasis and wound healing repair. The ability to control cell migration using nanoparticles could have substantial implications for developmental biology and provide new therapeutic avenues for chronic or catastrophic wound care.