P.T. Vernier Terahertz perturbation of the nanoscale biomembrane landscape

Terahert perturbation of the nanoscale biomembrane landscape

P.Thomas Vernier1 1Frank Reid Research Center for Bioelectrics, Old Dominion Universit , Norfolk, VA 20358 USA

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I. INTRODUCTION

NONTHERMAL stimulation and perturbation ith picosecond electric pulses and terahert electromagnetic radiation ma lead to ne , minimall invasive diagnostic and therapeutic procedures and to methods for remote monitoring and anal sis of biological s stems plants, animals, and humans. To optimi e utili ation of these tools e need an understanding of the underl ing bioph sical mechanisms. Sub-nanosecond ( 500 ps) electric pulses induce action potentials in neurons and cause calcium transients in neuroblastoma-glioma h brid cells, and in complementar molecular d namics simulations of phospholipid bila ers in intense electric fields membrane permeabili ation occurs in less than 1 ns (Fig. 1). Water dipoles in the interior of these model membranes align in the direction of the field, responding at terahert frequencies to field reversals. Sub-nanosecond lipid electropore formation is similar to that observed on longer time scales energ minimi ing intrusions of interfacial ater into the membrane interior and subsequent reorgani ation of the bila er into h drophilic, conductive structures. This suggests that membrane permeabili ation ma be the mechanism for the activation of neural cells b picosecond electric pulses.

II. RESULTS

Picosecond membrane reorgani ation in molecular simulations. Ho can this be? Since there is no h drogenbonded net ork in the intruding ater fingers, the effective rela ation time is much less than it is in bulk ater. The isolated ater molecules that stack up in the membrane interior during pore initiation have escaped their interfacial associations. A field-stabili ed ater column penetrating the membrane remains a lo er energ configuration for interfacial ater than the planar lipid- ater junction of an unperturbed bila er regardless of the 180-degree flips of the individual molecules making up the structures.

One might e pect that each picosecond reversal of the electric field direction ould undo hatever dipole rearrangements had occurred in the preceding c cle, ith no net effect, and that since the te tbook ater dipole rela ation time is on the order of 8 ps [1], ater molecule orientation should not be affected b s mmetrical electric field reversals occurring at 1 ps intervals. Molecular simulation results are contrar to these e pectations. S abili a ion of in ding a e in he applied elec ic field [2] is not reversed hen the field direction changes. Transbila er ater bridges gro , rather than shrink, c cle after c cle, and the phospholipid head groups follo .

Terahert spectral signature of electroporated cells. Electroporation (electropermeabili ation) increases the electrical conductivit of biological cell membranes and lo ers transport barriers for normall impermeant materials. The interior of the electroporated membrane contains ater, unlike the interior of an intact membrane, hich should create a signature for detection of the electropermeabili ed state. In a previous report, e described the use of terahert time-domain spectroscop to detect electroporation in human cells subjected to permeabili ing pulsed electric fields ith a commercial terahert , time-domain spectrometer [3]. We observed a higher absorption of terahert radiation b pulsee posed cells than in controls, consistent ith the intrusion of ater into the membrane into the cell through the permeabili ing structures presumed to be associated ith electroporation.

Fig. 1. Permeabili ation of POPC bila er in 500 GH alternating electric field. Water, then phospholipid head groups bridge the membrane interior in a ver high porating electric field ith polarit reversals ever picosecond. Multiple ater bridges appear, follo ed b head groups, in a fe tens of picoseconds.

REFERENCES

[1]. Buchner, R., J. Barthel, and J. Stauber. 1999. The dielectric rela ation of ater bet een 0 and 35 . Chem. Ph s. Lett. 306:57-63. [2]. Tokman, M., J. H. Lee, Z. A. Levine, M. C. Ho, M. E. Colvin, and P. T. Vernier. 2013. Electric field-driven ater dipoles: Nanoscale architecture of electroporation. PLoS ONE 8:e61111. [3]. Romeo, S., P. T. Vernier, and O. Zeni. 2018. Electroporation-induced cell modifications detected ith TH time-domain spectroscop . J Infrared Millim Terahert Wa es 39:854-862.

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