Abstract
A magnetically controlled elastically driven electroporation phenomenon, or magneto-elasto-electroporation (MEEP), is discovered while studying the interactions between core-shell magnetoelectric nanoparticles (CSMEN) and biological cells in the presence of an a.c. magnetic field. In this paper we report the effect of MEEP observed via a series of in-vitro experiments using core (CoFe2O4)-shell (BaTiO3) structured magnetoelectric nanoparticles and human epithelial cells (HEP2). The cell electroporation phenomenon and its correlation with the magnetic field modulated CSMEN are described in detail. The potential application of CSMEN in electroporation is confirmed by analyzing crystallographic phases, multiferroic properties of the fabricated CSMEN, influences of d.c. and a.c. magnetic fields on the CSMEN and cytotoxicity tests. The mathematical formalism to quantitatively describe the phenomena is also reported. The reported findings provide insights into the underlying MEEP mechanism and demonstrate the utility of CSMEN as an electric pulse-generating nano-probe in electroporation experiments with a potential application toward accurate and efficient targeted cell permeation.
Highlights
Electroporation in brief is the universal phenomenon of opening conductive pores on cell membrane when exposed to a millisecond to nanosecond electric pulse with tens of kV/cm intensity applied from a few microseconds to millisecond time scale at a sub-millimeter to micrometer distance[1,2,3,4,5,6]
Chang and Reese as well as several other researchers, have reported the closing of these nanopores after ~10 sec of electric field exposure when kept in an electrolyte, which clearly demonstrates that the hydrophobic tails of the phospholipids in the bilayer membrane tend to cluster again in a polar medium due to the hydrophobic effect and close the nanopore
The experiments and the analysis reported in this paper demonstrate that the core-shell magnetoelectric nanoparticle (CSMEN) retained the physical, electrochemical, magnetic, and piezoelectric properties associated with their respective core and shell components based on the corresponding diffraction patterns, zeta potential values, magnetic hysteresis loops, and piezoelectric force microscopic responses
Summary
Electroporation in brief is the universal phenomenon of opening conductive pores on cell membrane when exposed to a millisecond to nanosecond electric pulse with tens of kV/cm intensity applied from a few microseconds to millisecond time scale at a sub-millimeter to micrometer distance[1,2,3,4,5,6]. In 1990, Chang and Reese reported visual confirmations of the formation of various volcano-shaped pore openings of diameters varying from 20–120 nm within 40 ms of an applied RF electric field[28] In their experiments, Rae and Levis verified single cell electroporation by studying one volcanic-shaped nanopore on a cell membrane[29]. When placed within a sub-micrometer distance of a cell membrane, the continuous change of the surface potential of CSMEN under the influence of an a.c. magnetic field results in a cell’s transmembrane voltage change across the bilayer phospholipid membrane. The core-shell nano-composite structure studied enables novel multiferroic couplings between the magnetostrictive properties of the cobalt ferrite (CFO) core and the piezoelectric properties of the barium titanate (BT) shell, which results in modulation of the surface potential of the CSMENs directly by the externally applied a.c. magnetic field
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