Theoretical Studies Of Manipulating Biomolecules Confined Within Single-Walled Nanotubes By External Charges

Confinement of molecules inside nanoscale pores can lead to interesting properties and behaviors that differ from those of bulk systems.Some examples are enhanced catalysis and enhanced stability of the native structure of proteins,new folding mechanisms of proteins,transition of ionic liquid from liquid to high-melting-point crystal,the ordered water structure,extrafast motion of water molecules,and excellent on-off gating behavior of single-file water chain.Furthermore,when the molecules are confined in nanosized water droplets,their structures,hydrophobic and ionic interactions differ from those in bulk water.Recently,confinement of molecules inside nanoscale pores has become an important method for exploiting new dynamics not happened in bulk systems and for fabricating novel structures.However,once the molecules that are encapsulated in nanopores,it is difficult to control with respect to their position and activity.Numerous studies have examined the translocation of charged and uncharged molecules along nanochannels, such as using an electric field to drive the charged RNA molecules through nanopores, making use of capillary force to draw decane molecules into a single-walled carbon nanotube(SWNT) and temperature difference to drive their transport through the SWNT,pumping gas molecules through the Lennard-Jones interaction between gas molecules and the wall of nanotube,driving a water flow through the coupling between electron and the dipole of water molecules.However,to our knowledge,there is no report on the controllable manipulation of the biomolecules in a nanopore both in space and time.In this thesis,making use of "Coulombic Dragging" at nanoscale,we proposed an approach towards this direction on the basis of molecular dynamics(MD) simulations, benefiting from the single-walled structure of the nanotube and the unique properties of water.We used the SWNT as an example for the demonstration,because carbon nanotubes have outstanding potentials for applications in nanoscale sensors/devices/machines.We have shown that the positions of the peptides with aqueous liquids inside a single-walled nanotube can be controllably manipulated by a charge or a group of charges outside the nanotube.The two peptides we used in our simulations are the Alzheimer's-disease-related peptides,one has charged residues and charge-neutral as a whole,and another one has no charged residues.We have performed two kinds of simulations to demonstrate our designs:(1) the first kind of simulation:the peptide which has charged residues was encapsulated in the SWNT,the other space of SWNT was fully filled with water.A group of external charges were located at 3.5(?) from the SWNT wall.The other space outside the SWNT is in vacuum.We found we could manipulate the position of this peptide through manipulating the position of the external charges.This remarkable manipulation ability is attributed to the single-walled structure of the nanotube that the electrostatic interactions of charges inside and outside the single-walled nanotube are strong enough.As a result,we can manipulate the peptide through "Coulombic Dragging".Due to the intense random-collisions between peptide and water molecules,we must use a group of external charges to tightly trap the charged group of the peptide.Otherwise,the manipulation will be unsuccessful.(2) The second kind of simulation:a peptide which has no charged residues was solvated in a nanosized water droplet.This drop of the peptide-water mixture was encapsulated in the SWNT.A single charge was allocated above the peptide-water mixture at 3.5(?) from the SWNT wall.The other space of this system was in vacuum.We found we could manipulate the position of the peptide-water mixture through manipulating the position of the extemal charge.This remarkable manipulation ability is attributed to the unique properties of water molecules:although the water molecule is charge-neutral as a whole, it has a large dipole moment.Thus the external charge can induce the dipole-orientation ordering of water confined in the nanochannel,as a result,water has a strong electrostatic interaction with the external charge.Making use of this strong electrostatic interaction,we can manipulate the peptide-water mixture through "Coulombic Dragging".Moreover,because of the atomic smoothness of the SWNT wall,the friction between the peptide-water mixture and the SWNT wall is small,when the peptide-water mixture was moving along the SWNT.On the basis of these simulation results,we have proposed two designs to manipulate the biomolecules with aqueous liquids confined within single-walled nanotubes by using the charge(s) outside the tube.The first design is the direct manipulation of the biomolecules:if the biomolecule has charged residue(s),we can controllably manipulate the biomolecule by manipulating a group of charges outside the nanotube,even the nanotube is fully filled with water;The second design is the indirect manipulation of the biomolecules(manipulate the biomolecule through manipulating the biomolecule-water mixture):experimentally,the drop of biomolecule-water mixture used in this simulation can be realized through spontaneous accumulation of the water molecules surrounding the biomolecule in an environment with moderate humidity.Then we can manipulate the position of the biomolecule through manipulating the position of the biomolecule -water mixture,by using one external charge.We note that,when the biomolecule is a larg molecule such as a protein,the effective value of the external charge required for successful manipulation should be larger.In the case where the probability of the successful manipulations by a single charge is low,we can use a series of charges, which can greatly enhance the probabilities.We also presented the detailed discussions about the practical feasibility of our designs.(1) Experimentally,there are at least two ways to realize the external charge(s) on the facilities:a bias voltage applied on an AFM/STM tip and the AFM/STM tip modified with the compounds carrying charge(s).These kinds of tips should work in vacuum or in air under low humidity conditions.Otherwise,the interactions of the extemal charge(s) with the peptide and water inside the nanotube will decrease remarkably due to the screening effect of the solution on the extemal charge(s). Furthermore,the extemally charged atom(s) may not be brought close enough to the nanotube.(2) The electrostatic forces which the peptide and the water inside the nanochannel exert on the external charge(s) were at magnitude from pN to nN,which fell within the working range of many existing techniques such as STM and AFM.So we can manipulate the biomolecules by using STM or AFM.(3) We found that the speed of the external charge had a remarkable influence on the manipulation.As the speed of the external charge decreases,the probabilities for these unsuccessful eases decrease.Considering that the speed of the external charge in our simulation is very high,the efficiency for successful manipulation may even be higher for a much lower speed under experimental conditions.(4) In practical applications,the screening effect on the electric field must be considered.The external charges required for these manipulations are quite small,which are still available after taking into account the screen effect of many nanotubes.The screening factor depends on the particular nanochannels used.The manipulation becomes more effective for a smaller screening effect.This is particularly true when using insulator nanochannels,which may be fabricated in the near future.(5) We performed another simulation and found that:when a peptide was near the entrance of a carbon nanotube in a water solute environment,it could be spontaneously inserted into the nanotube.The van der Waals and hydrophobic forces were responsible for the insertion process.This finding should have wide applications such as the encapsulation of biomolecules into the nanotube,and the nanotube-based drug delivery.Experimentally,the determination of the positions of the molecules encapsulated in the nanopores with respect to time is important for controlling the interactions and chemical reactions of the molecules.Although the molecules used in our simulation is the biomolecules,we believe our designs can be used to manipulate lots of other molecules,regardless if there is any charged residue on the molecules.By using these designs,we can controllably move two biomolecules together convenient for the interaction or chemical reactions of them.Our designs are expected to serve as lab-in-nanotube for the interactions and chemical reactions of molecules especially biomolecules(because most of the biomolecules have charged residues;moreover,it is easy for the water molecules spontaneously accumulate surrounding the biomolecules), and have wide applications in nanotechnology and biotechnology.Water molecules confined in nanoscale channels usually exhibit dynamics different from bulk water.Understanding and controlling the transport of water across nanochannels is of great importance for designing novel molecular devices and has wide applications in nanotechnology.Experimentally,defects are common in nanochannels fabricated.By co-working with Songyan Li,we studied the water permeation across a (6,6) single-walled carbon nanotube with 5/7 pair topological defects based on molecular dynamics simulations.We found that:as the case of water in the(6,6) nanotube with no defect,the(6,6) nanotube with defects was fully filled with water,and the water molecules in the nanotube formed single-filed structure;the impact on the water permeation was negligible when the density of the defects was small while a significant reduction of the water permeation was observed when the density of the defects was high;the one-dimensional diffusion constant was also calculated and was found to share a similar behaviour as the flow;as the number of defects increased,the average number of water molecules and hydrogen bonds inside the nanotube slowly increased and then remained almost unchanged;when the number of defects in nanotube were more than three,the height of the PMF(potential of mean force) barrier increased remarkably,and the flow decreased power exponentially with respect to the height of barrier.Furthermore,an exponential law was found on the water flow across the channel with respect to the water-nanotube potential well.This result suggested that the smaller flow derived from the deeper water-nanotube potential well.Considering the unavoidable defects in the fabrications of carbon nanotubes,rough internal surfaces of many of the other kinds of nanochannels,and the complex structure of biological channel,these findings should be helpful in the understanding of the water permeation across nanotube as well as biological channel,and be useful in designing efficient artificial nanochannel.