Nuclear transport by laser-induced pressure transients

Tai Yuan David Lin, Daniel J. McAuliffe, Norm Michaud, Hong Zhang, Shun Lee, Apostolos G. Doukas, Thomas J. Flotte

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Purpose. Control of the transport of molecules into the nucleus represents a key regulatory mechanism for differentiation, transformation, and signal transduction. Permeabilization of the nuclear envelope by physical methods can have applications in gene therapy. Laser-induced pressure transients can produce temporary aqueous pores analogous to those produced by electroporation and that the cells can survive this procedure. In this study, we examine the role of the pressure transients in creating similar pores in the nuclear envelope. Methods. The target human peripheral blood mononuclear cells in a 62 μM 72 kDa fluoresceinated dextran solution were exposed to the pressure transients generated by laser ablation. An in vitro fluorescence confocal microscope was used to visualize and quantify the fluoresceinated dextran in the cytoplasmic and nuclear compartments. Results. In contrast to electroporation, the pressure transients could deliver 72 kDa fluoresceinated dextrans, which are normally excluded by the nucleus, across the nuclear envelope into the nucleus. In addition to creating pores in the plasma membrane, temporary pores were also created in the nuclear envelope following exposure to pressure transients. Conclusion. The production of temporary nuclear pores could provide a unique resource for drug-delivery and gene therapy.

Original languageEnglish (US)
Pages (from-to)879-883
Number of pages5
JournalPharmaceutical research
Volume20
Issue number6
DOIs
StatePublished - Jun 1 2003

Keywords

  • Ablation
  • Drug delivery
  • Electroporation
  • Nuclear envelope
  • Shock waves

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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