Nucleic acid transport through carbon nanotube membranes

Abstract

We study the electrophoretic transport of single-stranded RNA molecules through 1.5-nm-wide pores of carbon nanotube membranes by molecular dynamics simulations. From Ϸ170 individual RNA translocation events analyzed at full atomic resolution of solvent, membrane, and RNA, we identify key factors in membrane transport of biopolymers. RNA entry into the nanotube pores is controlled by conformational dynamics, and exit by hydrophobic attachment of RNA bases to the pores. Without electric field, RNA remains hydrophobically trapped in the membrane despite large entropic and energetic penalties for confining charged polymers inside nonpolar pores. Differences in RNA conformational flexibility and hydrophobicity result in sequence-dependent rates of translocation, a prerequisite for nanoscale separation devices.B iopolymer translocation across membranes is essential in many important biological processes, such as gene expression and protein targeting. Electrostatic membrane potentials play a critical role in biopolymer transport, as demonstrated for the import of unfolded proteins into the mitochondrial matrix (1). Electrostatically driven membrane translocation is also increasingly used to measure the properties of single polymers (2-6). The blockage of ionic currents during electric-field-driven translocation of individual nucleic acid molecules through membrane-inserted ␣-hemolysin channels (7) was shown to depend on length, base composition, and sequence (2, 3), suggesting possible applications in ultrafast and single-molecule sequencing of nucleic acids. However, the transport of polymers through membrane-bound protein channels (2-6) is complicated by specific molecular interactions with the highly structured pores. Nonbiological membranes and pores (8, 9), such as carbon nanotubes assembled into hexagonally packed two-dimensional arrays (10, 11), provide simple, controllable, and potentially more robust systems to study fundamental aspects of membrane translocation. Computer simulations suggest that carbon nanotubes accommodate rapid water (12-14) and proton (15) flow and take up nucleic acids (16), despite their highly restricted pore size and low polarity. Water filling of nanotubes (17, 18), as well as the flow of an aqueous electrolyte through carbon nanotube membranes (11) and the transport of DNA (19) through a single carbon nanotube were also observed experimentally.Here, we report the results of all-atom molecular dynamics simulations of RNA translocation through carbon nanotube membranes in explicit solvent. These simulations allow us to study membrane translocation at atomic detail, extending earlier studies of coarse-grained polymer translocation models (20-23). By including detailed descriptions of water and ions, the simulations capture electrostatic and hydrophobic solvation effects on the translocation processes and permit a detailed study of sequence dependences. As we will show, hydrophobic interactions of the bases with the nanotube pores can transiently trap RNA at the pore walls. To analyze t...

Correlated movements of ions and water in a nanochannel

“…One example is the transport of microscopic particles, including atoms, ions, molecules, and colloids, through nanochannels, which is significant for fundamental biological processes and industrial applications as well. Examples include molecular or ionic permeation in zeolites [1,2], in carbon nanotubes [3,4], in aquaporins [5] and in ion channels [6][7][8]. In the present paper we report on molecular dynamics studies of the microscopic nonequilibrium transport of ions and water molecules through a nanochannel which shares structural similarities with a known biological potassium channel [9,10].…”

Carbon nanotube-based nano-fluidic devices

“…Very fast water transport through CNTs was predicted, because of the frictionless motion. Following the pioneering work on water molecule transport, the translocations of more complicated molecules, such as long chain polymer molecules 44 , DNA 45 and RNA 46 , through CNT were simulated as well. Simulations revealed that DNA molecules enter CNT spontaneously with the aid of van der Waals and hydrophobic interaction forces 47 and the translocation events can be driven by an electric field.…”

“…59 DNA has been passed through a 100 nm diameter carbon nanotube 60 and 50 nm wide hydrophilic channels. 61 It seems counter-intuitive that hydrophilic DNA would enter the hydrophobic interior of a SWCNT but theoretical simulations show that both RNA 62 and DNA 63 will translocate through 1.5 to 2 nm diameter tubes.…”

Final report : LDRD project 79824 carbon nanotube sorting via DNA-directed self-assembly.

“…They found that the ssDNA either inserted into the nanotube or wrapped around the outside, depending on the SWNT diameter. Several other groups performed further simulations on the encapsulation of DNA, RNA, and other biomolecules into SWNTs [21,22,23,24]. We are not aware of any detailed studies of the adsorption of nucleic acids on the outside of SWNTs.…”