NER: Intracellular Nanoprobes for Physical Manipulation of Cells

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CBET-0707969 Winter The applicant is creating intracellular nanoprobes for the physical manipulationof cells using magnetic nanoparticles (i.e., supraparamagnetic iron oxide nanoparticles(SPIONs)). SPIONs are excellent candidate materials for mechanical cellular nanoprobesbecause they can serve as physical actuators, producing a controlled, investigator-triggeredforce in response to a magnetic field. Previously, SPIONs encapsulated in magneticmicrospheres have been used to examine the response of cells to extracellular force. Thesestudies demonstrated that the cytoskeleton, a biopolymer network responsible for the mechanicalintegrity of cells, is part of an elaborate mechanotransduction system that can influence manycell functions. However, these studies use large particles, nearly half the size of a cell, whichindirectly interface with the cytoskeleton through extracellular cell surface receptors. Althoughsome attempts have been made to use smaller SPIONs inside a cell, these methods rely onparticle endocytosis for delivery. Particles remain trapped in endosomes, unable to interact withcytoplasmic structures. Thus, the potential to manipulate the cytoskeleton directly remainslargely 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 roleof 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.