Small Interfering RNA Transfection Across a Phospholipid Membrane

ORAL

Abstract

Small interfering RNA (siRNA) molecules play a pivotal role in silencing gene expression via the RNA interference mechanism. We have performed steered MD simulations to study the transfection of a bare siRNA and siRNA/Oleic Acid (OA) complex across the dipalmitoylphosphatidycholine (DPPC) bilayer at T = 323 K. Bare siRNA induces the formation of frustrated lipid gel domains, whereas in the presence of siRNA/OA complex the membrane is found to be in the liquid-ordered phase. In both cases the stress profiles across the membrane indicate that the membrane is under tension near the head groups and highly compressed at the water-hydrophobic interface. During transfection, the membrane is deformed and the lateral stress is significantly lowered for the bare siRNA and siRNA/OA complex. The bare siRNA transfects through a lipid-nanopore of hydrophilic head-groups and hydrophobic carbon chains, whereas the siRNA/OA complex transfects through a lipid-nanopore of hydrophilic head groups.

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Authors

  • Ken-ichi Nomura

    • Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, University of Southern California, Los Angeles, California

  • Van Ngo

    • Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, University of Southern California, Los Angeles, California

  • Amit Choubey

    • Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, University of Southern California, Los Angeles, California

  • Rajiv Kalia

    • Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, University of Southern California, Los Angeles, California

  • Aiichiro Nakano

    • Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, University of Southern California, Los Angeles, California

  • Priya Vashishta

    • Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, University of Southern California, Los Angeles, California