The alteration of cellular functions by anchoring macromolecules to specified organelles may reveal a new area of therapeutic potential and clinical treatment. In this work, a unique phenotype was evoked by influencing cellular behavior through the modification of subcellular structures with genetically targetable macromolecules. These fluorogen-functionalized polymers, prepared via controlled radical polymerization, were capable of exclusively decorating actin, cytoplasmic, or nuclear compartments of living cells expressing localized fluorgen-activating proteins. The macromolecular fluorogens were optimized by establishing critical polymer architecture-biophysical property relationships which impacted binding rates, binding affinities, and the level of internalization. Specific labeling of subcellular structures was realized at nanomolar concentrations of polymer, in the absence of membrane per-meabilization or transduction domains, and fluorogen-modified polymers were found to bind to protein intact after delivery to the cytosol. Cellular motility was found to be dependent on binding of macromolecular fluorogens to actin structures causing rapid cellular ruffling without migration. (C) 2015 Elsevier Ltd. All rights reserved.
Genetically targeted fluorogenic macromolecules for subcellular imaging and cellular perturbation
Creators
Andrew J. D. Magenau - Carnegie Mellon University
Saumya Saurabh - Carnegie Mellon University
Susan K. Andreko - Carnegie Mellon University
Cheryl A. Telmer - Carnegie Mellon University
Brigitte F. Schmidt - Carnegie Mellon University
Alan S. Waggoner - Carnegie Mellon University
Marcel P. Bruchez - Carnegie Mellon University
Publication Details
Biomaterials, v 66
Publisher
Elsevier
Number of pages
8
Grant note
U54GM103529 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
McWilliams Graduate Fellowship
U54GM103529 / NIH, through the Technology Centers for Networks and Pathways program; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Resource Type
Journal article
Language
English
Academic Unit
Materials Science and Engineering
Web of Science ID
WOS:000359328200001
Scopus ID
2-s2.0-84938090599
Other Identifier
991019168043004721
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