Matthew Becton

Designing Nanoparticle Translocation through Cell Membranes by Varying Amphiphilic Polymer Coatings

Nanoparticle (NP)-assisted drug delivery has been emerging as an active research area. Understanding and controlling the interaction of the coated NPs with cell membranes is key to the development of the efficient drug delivery technologies and to the management of nanoparticle-related health and safety issues. Cellular uptake of nanoparticles coated with mixed hydrophilic/hydrophobic polymer ligands is known to be strongly influenced by the polymer pattern on the NP surface and remains open for further exploration. To unravel the physical mechanism behind this intriguing phenomenon, here we perform dissipative particle dynamics simulations to analyze the forces and efficacy time as the copolymer-coated NPs pass through the lipid bilayer so as to provide better design of coated NPs for future drug delivery applications. Four characteristic copolymer ligands are constructed to perform the simulations: hydrophilic-hydrophobic (AB), hydrophobic-hydrophilic (BA), hydrophobic-hydrophilic-hydrophobic-hydrophilic (BABA), and a random pattern with hydrophilic and hydrophobic beads. We mainly study the critical force and potential of mean force required for entering inside of the lipid bilayer and penetration force to pass all the way through the cell membrane as well as the translocation time for these patterned NPs across the bilayer. Through copolymer ligand pattern designing, we find a suitable nanoparticle candidate with a specific polymer coating pattern for drug delivery. These findings provide useful guidelines for the molecular design of patterned NPs for controllable cell penetrability and help establish qualitative rules for the organization and optimization of copolymer ligands for desired drug delivery.

Thermal Gradients on Graphene to Drive Nanoflake Motion

Thermophoresis has been emerging as a novel technique for manipulating nanoscale particles. Materials with good thermal conductivity and low surface friction, such as graphene, are best suited to serve as a platform for solid-solid transportations or manipulations. Here we employ nonequilibrium molecular dynamics simulations to explore the feasibility of utilizing a thermal gradient on a large graphene substrate to control the motion of a small graphene nanoflake on it. Attempts to systematically investigate the mechanism of graphene-graphene transportation have centered on the fundamental driving mechanism of the motion and the quantitative effect of significant parameters such as temperature gradient and geometry of graphene on the motion of the nanoflake. Simulation results have demonstrated that temperature gradient plays the pivotal role in the evolution of the motion of the nanoflake on the graphene surface. Also, the geometry of nanoflakes has presented an intriguing signature on the motion of the nanoflake, which shows the nanoflakes with a circular shape move slower but rotate faster than other shapes with the identical area. It reveals that edge effects can stabilize the angular motion of thermophoretically driven particles. An interesting relation between the effective initial driving force and temperature gradient has been quantitatively captured by employing the steered molecular dynamics. These findings will provide fundamental insights into the motion of nanodevices on a solid surface due to thermophoresis, and will offer the novel view for manipulating nanoscale particles on a solid surface in techniques such as cell separation, water purification, and chemical extraction.

Molecular Dynamics Study of Programmable Nanoporous Graphene

AbstractNanoporous graphene has emerged as a powerful alternative to conventional membrane filters and gained an appreciable popularity in a variety of applications because of its many remarkable and unique properties. Careful regulation of the size and density of nanopores can generate graphene membranes with controllable selectivity and flow rate, thereby greatly enhancing the potential marketability of graphene-based membranes. In this research, molecular dynamics simulation is employed to systematically investigate the mechanistic and quantitative effect of significant parameters such as temperature, impact energy, strain, and pore density on the nanopore morphology of graphene by impacting fullerenes into a graphene sheet. Simulation results have demonstrated that both nanopore size and morphology in a graphene sheet can be tailored by carefully controlling the energy of the impact cluster, the temperature of the environment, and the strain applied on the graphene sheet. This serves as a conceptual g...

Controlling nanoflake motion using stiffness gradients on hexagonal boron nitride

Durotaxis has been emerging as a novel technique for manipulating directional motion of nanoscale particles. Two-dimensional materials with low surface friction, such as hexagonal boron nitride (hBN), are well-suited to serve as a platform for solid–solid transportations or manipulations. Here we employ molecular dynamics simulations to explore the feasibility of utilizing a stiffness gradient on a large hBN substrate to control the motion of a small hBN or graphene nanoflake on it. Our attempts to systematically investigate the mechanism of durotaxis-induced transportation are centered on the fundamental driving mechanism of the motion and the quantitative effect of significant parameters such as stiffness gradient, substrate temperature, and material of the nanoflake on its motion. Simulation results have demonstrated that, while the stiffness gradient plays a pivotal role in the evolution of the motion of the nanoflake on the substrate surface, the temperature of the substrate greatly influences the behavior of the nanoflake as well. There is no significant difference in directional motion between hBN and graphene nanoflakes on the hBN substrate. An interesting relation between the effective driving force and the stiffness gradient has been quantitatively captured by employing steered molecular dynamics. These findings will provide fundamental insights into the motion of nanodevices on a solid surface due to durotaxis, and will offer a novel view for manipulating directional motion of nanoscale particles on a solid surface.

Artificial biomembrane morphology: a dissipative particle dynamics study

Artificial membranes mimicking biological structures are rapidly breaking new ground in the areas of medicine and soft-matter physics. In this endeavor, we use dissipative particle dynamics simulation to investigate the morphology and behavior of lipid-based biomembranes under conditions of varied lipid density and self-interaction. Our results show that a less-than-normal initial lipid density does not create the traditional membrane; but instead results in the formation of a ‘net’, or at very low densities, a series of disparate ‘clumps’ similar to the micelles formed by lipids in nature. When the initial lipid density is high, a membrane forms, but due to the large number of lipids, the naturally formed membrane would be larger than the simulation box, leading to ‘rippling’ behavior as the excess repulsive force of the membrane interior overcomes the bending energy of the membrane. Once the density reaches a certain point however, ‘bubbles’ appear inside the membrane, reducing the rippling behavior and eventually generating a relatively flat, but thick, structure with micelles of water inside the membrane itself. Our simulations also demonstrate that the interaction parameter between individual lipids plays a significant role in the formation and behavior of lipid membrane assemblies, creating similar structures as the initial lipid density distribution. This work provides a comprehensive approach to the intricacies of lipid membranes, and offers a guideline to design biological or polymeric membranes through self-assembly processes as well as develop novel cellular manipulation and destruction techniques.

Effects of nanobubble collapse on cell membrane integrity

Recent studies have shown that ultrasound is used to open drug-carrying liposomes to release their payloads; however, a shockwave energetic enough to rupture lipid membranes can cause collateral damage to surrounding cells. Similarly, a destructive shockwave, which may be used to rupture a cell membrane in order to lyse the cell (e.g., as in cancer treatments) may also impair or destroy nearby healthy tissue. To address this problem, we use dissipative particle dynamic (DPD) simulation to investigate the addition of a cavitation bubble between the shockwave and the model cell membrane to alter the shockwave front, allowing low-velocity shockwaves to specifically damage an intended target. We focus specifically on a spherical lipid bilayer model, and note the effect of shockwave velocity, bubble size, and orientation on the damage to the model cell. We show that a cavitation bubble greatly decreases the necessary shockwave velocity required to damage the lipid bilayer and rupture the model cell. The cavitation bubble focuses the kinetic energy of the shockwave front into a smaller area, inducing penetration at the edge of the model cell. With this work, we provide a comprehensive approach to the intricacies of model cell destruction via shockwave impact, and hope to offer a guideline for initiating targeted cellular destruction using induced cavitation bubbles and low-velocity shockwaves.