Page 56 - ASME_NEMB_2016_Program

Technical Program TRACK 4

after nanoneedle insertion and the safety associated with this approach cient interaction between particles regardless of their spatial position or the
must be elucidated to further advance these platforms. Biological barriers processors they reside in within the computing cluster. The third interaction
serve to impede the delivery of biologics, for example: for nucleic acids domain that we introduce is the continuum space domain which allows com-
to be effective, they must be shuttled in their active form to the cytosol or munication between particles or between particles and their environment
nucleus bypassing the cell membrane and endolysosomal compartment. via diffusion or wave propagation. Currently the appropriate equations are
Currently, the in vivo delivery of nucleic acids remains impaired by issues solved by utilizing the explicit finite difference algorithm. The program allows
of safety, limited site accessibility, inadequate scalability, and inefficient particles from the network domain and spatial domain to interact via the
transfection. The direct nanoinjection of nucleic acids into the cytosol of continuum domain.
cells successfully addressed these issues. Nanoneedles did not induce any
significant acute inflammation or alteration in the normal tissue architecture Users can develop their own customized interacting domains based on the
or cellular ultrastructure. Nanoinjection permits the delivery of a payload to three C++ domain classes. Programming employing these three domains is
a confined area, effectively impacting only a specific set of cells while avoid- made user friendly as the computational environment provides classes to
ing areas of the tissue that are not of interest. This localized transfer of pay- easily and efficiently access the interacting particles. These classes are de-
loads enables to temporarily alter tissue structure and function by initiating signed to allow users to generate subclasses for specific problems. In addi-
biologically driven cellular processes (i.e., angiogenesis) in live tissues. tion, particles have properties that can adapt and be altered throughout the
Nanoporous silicon nanoneedles were produced using metal-assisted course of the simulation. The code is designed to accommodate complex
chemical etching to obtain needles with tip diameter of <50 nm, 5µm length, particle behaviors while the particles can store their individual properties
and 600nm base diameter. We investigated their interface with cells using such as mass, size, and electrical charge.
electron and confocal microscopy and used quantum dot to illustrate the
ability of nanoneedles to achieve cytosolic delivery. In addition, a payload The code can be used in numerous cases. The spatial domain allows users
of siRNA and DNA was used to demonstrate the efficient delivery of func- to simulate common short-range MD simulations. Users can also easily sim-
tional nucleic acids in vitro and in vivo. Microscopy techniques revealed ulate more complex scenarios such as diffusion of cell membrane proteins.
how nanoneedles interacted with the cells and permitted a kinetic study to The network domain allows user to simulation long distance protein-protein
provide insight on how nanoneedles gained access to the cytosol of cells interactions while the continuum space allows simulation of chemotaxis.
and induced the remodeling of the nuclear envelope. Furthermore, we com-
pared the seeding of cells over a nanoneedles substrate with the forceful
admini¬¬stration of nanoneedles to highlight the similarities and differences 4-7
between the two interfacing strategies. In both cases the nanoneedles
gained access to the cytosol but completed this process over different time- MOLECULAR INTERACTIONS AND SIMULATIONS
scales, with forceful nanoinjection gaining access quicker. Using quantum
dots as a model payload enabled the monitoring of the direct cytosolic Hidalgo 4:00pm - 5:40pm
delivery of nanoparticles within the cell. In addition, these nanoneedles al-
lowed for the sensing of intracellular pH without inducing apoptosis demon-
strating their successful negotiation of the endolysosomal system. Session Organizer: Sinan Keten, Northwestern University, Evan-
The delivery of nucleic acids was assessed using GAPDH siRNA, that was ston, IL, United States
successfully delivered intracellularly by the nanoneedles, achieving a >>90%
knockdown efficiency. Co-loading of Cy3-siRNA and a GFP DNA plasmid 4:00pm Multiscale Modeling of Ebola Virus Glycoprotein
demonstrated that nanoneedles co-transfected cells nearly at 100% efficien-
cy. In vivo studies demonstrated that nanoinjection yielded localized delivery Technical Presentation. NEMB2016-6028
of the payload to the superficial layer of various tissues. The nanoinjection
of VEGF-165 triggered neovascularization and induced a localized 6-fold
increase in blood perfusion exhibiting functional new vessel formation. In Ashley Guy, Alan Bowling, University of Texas at Arlington, Arling-
summary, nanoneedles represents a promising delivery strategy able to ton, TX, United States
interface with cells and tissues with minimal toxicity to deliver sensitive bio-
active payloads. This work investigates the application of a multiscale method to the model-
ing of proteins in dynamical simulations. High-resolution protein simulations
12:50pm Multidomain Particle Dynamics Toolkit HPC are defined at the nanoscale and integrated at the femtoscale. These na-
noscale simulations infamously require significant computational resources
Technical Presentation. NEMB2016-6024 to generate even modest time evolutions due to bottlenecks in the forward
dynamics: point-wise potential calculations and evaluation of the equations
of motion. The goal of the work is to reduce the computation time associat-
Vi Q., Ha, George Lykotrafitis, University of Connecticut, Storrs, CT, ed with solving the equations of motion.
United States
An existing method to reduce computation time is to use the over-damped
A large-scale, fast paced, lightweight, and easily customizable C++ particle Langevin equation, which assumes a large damping ratio and eliminates the
dynamics engine designed to run on distributed-memory parallel computing mass terms from the equations of motion. However, recent work has empir-
clusters is introduced. It uses message passing interface (MPI) distributions ically observed underdamped behavior in nanoscale systems using optic
for parallel computing operations and at the same time is intuitive and user tweezers, showing that the mass term may not be eliminated. Our method
friendly. It also employs a pointer system that can easily access all suitable retains the mass terms while providing greater savings than the massless
components of the molecular dynamics (MD) engine for customization. approximation.
The program currently has three main sets of interaction domains. The first
set is a spatial domain distributed accordingly to available processors for Coarse graining methods reduce model resolution by eliminating small
short-range MD simulations. The spatial decomposition utilizes the linked discrete bodies, like hydrogen ions, or grouping clusters of rigidly attached
list method to build a very efficient cell list algorithm. The spatial decom- bodies into a single approximate body. These approaches simplify the
position algorithm allows extreme fast paced and efficient computations of model and allow for larger integration time steps. Our method builds upon a
large-scale MD simulations with interactive potentials within a cut off radius. coarse graining approach to further reduce computation time.
However, the cell list method cannot be employed in interactions between
particles separated at distances larger than the cut-off distance without The multiscale method used in this work scales the terms in the equations of
56 losing computational efficiency. To address this problem we developed a motion and brings those terms into the same order of magnitude. The the-
second interaction domain, the global network domain. The global network oretical justification comes from a perturbation method showing that many
represent particles as nodes and connects them via edges. This allows effi- of the active forces cancel. If two forces cancel without producing a net