Controlled aggregation of ferritin to modulate MRI relaxivity

Kevin M. Bennett, Erik M. Shapiro, Christopher H. Sotak, Alan P. Koretsky

Research output: Contribution to journalArticle

  • 34 Citations

Abstract

Ferritin is an iron storage protein expressed in varying concentrations in mammalian cells. The deposition of ferric iron in the core of ferritin makes it a magnetic resonance imaging contrast agent, and ferritin has recently been proposed as a gene expression reporter protein for magnetic resonance imaging. To date, ferritin has been overexpressed in vivo and has been coexpressed with transferrin receptor to increase iron loading in cells. However, ferritin has a relatively low T 2 relaxivity (R 2 ≈ 1 mM -1s -1) at typical magnetic field strengths and so requires high levels of expression to be detected. One way to modulate the transverse relaxivity of a superparamagnetic agent is to cause it to aggregate, thereby manipulating the magnetic field gradients through which water diffuses. In this work, it is demonstrated by computer simulation and in vitro that aggregation of ferritin can alter relaxivity. The effects of aggregate size and intraaggregate perturber spacing on R 2 are studied. Computer modeling indicates that the optimal spacing of the ferritin molecules in aggregate for increasing R 2 is 100-200 nm for a typical range of water diffusion rates. Chemical cross-linking of ferritin at 12 Å spacing led to a 70% increase in R 2 compared to uncross-linked ferritin controls. To modulate ferritin aggregation in a potentially biologically relevant manner, ferritin was attached to actin and polymerized in vitro. The polymerization of ferritin-F-actin caused a 20% increase in R 2 compared to unpolymerized ferritin-G-actin. The R 2-value was increased by another 10% by spacing the ferritin farther apart on the actin filaments. The modulation of ferritin aggregation by binding to cytoskeletal elements may be a useful strategy to make a functional reporter gene for magnetic resonance imaging.

Original languageEnglish (US)
Pages (from-to)342-351
Number of pages10
JournalBiophysical Journal
Volume95
Issue number1
DOIs
StatePublished - Jul 1 2008
Externally publishedYes

Profile

Ferritins
Actins
Iron
Magnetic Resonance Imaging
Magnetic Fields
Water
Proteins
In Vitro Techniques
Transferrin Receptors
Actin Cytoskeleton
Reporter Genes
Polymerization
Computer Simulation
Contrast Media
Gene Expression

ASJC Scopus subject areas

  • Biophysics

Cite this

Controlled aggregation of ferritin to modulate MRI relaxivity. / Bennett, Kevin M.; Shapiro, Erik M.; Sotak, Christopher H.; Koretsky, Alan P.

In: Biophysical Journal, Vol. 95, No. 1, 01.07.2008, p. 342-351.

Research output: Contribution to journalArticle

Bennett, KM, Shapiro, EM, Sotak, CH & Koretsky, AP 2008, 'Controlled aggregation of ferritin to modulate MRI relaxivity' Biophysical Journal, vol 95, no. 1, pp. 342-351. DOI: 10.1529/biophysj.107.116145
Bennett KM, Shapiro EM, Sotak CH, Koretsky AP. Controlled aggregation of ferritin to modulate MRI relaxivity. Biophysical Journal. 2008 Jul 1;95(1):342-351. Available from, DOI: 10.1529/biophysj.107.116145

Bennett, Kevin M.; Shapiro, Erik M.; Sotak, Christopher H.; Koretsky, Alan P. / Controlled aggregation of ferritin to modulate MRI relaxivity.

In: Biophysical Journal, Vol. 95, No. 1, 01.07.2008, p. 342-351.

Research output: Contribution to journalArticle

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