Page 30 - ASME_NEMB_2016_Program

Technical Program TRACK 2

tential that the anti-obesity and anti-diabetic actions observed from nDS-ad- Keynote. NEMB2016-6010
ministered GC-1 could be translated to humans.
Sean Sun, Johns Hopkins University, Baltimore, MD, United States
10:40am Nanowarming of Arteries
Animal cells are mechanically complex, but enough experimental knowl-
Technical Presentation. NEMB2016-6136 edge have been accumulated for significant quantitative understanding. We
discuss active forces and active mass fluxes that are important for determin-
Navid Manuchehrabadi, Zhe Gao, Jinjin Zhang, Hattie Ring, Qi ing cell shape and cell volume in a variety of environments. We consider ac-
Shao, Michael McDermott, Feng Liu, Yung Chung Chen, Alex tive mechanical response of the cell to external mechanical as well as chem-
ical perturbations, and describe how to include these active processes in a
Fok, Michael Garwood, university of minnesota, minneapolis, MN, mechanochemical model. From fundamental force balance considerations,
United States, Kelvin G.M. Brockbank, Department of Bioengi- we derive a set of mathematical equations to compute cell shape and cell
neering, Clemson University, Clemson, SC, United States, Christy L. volume for a given biochemical content. The application of this framework
Haynes, University of Minnesota, Minneapolis, MN, United States, for understanding single cell mechanics, tissue cell dynamics and collective
John Bischof, Univ Of Minnesota, Minneapolis, MN, United States cell motility will be discussed. In particular, collective dynamics in confluent
cell monolayers will be highlighted.
There is an ongoing clinical need for long term banking of transplantable tis-
sues such as arteries, veins, skin, heart valves and cartilage. One approach 10:00am The evolution of multivalent nanoparticle adhesion
to this is vitrification of tissue in a glassy vs. crystalline state at temperatures revealed using Nano Adhesive Dynamics Simulations
below the glass transition. Unfortunately, rewarming these tissues from the
vitrified state requires both fast and uniform thawing to avoid crystallization Technical Presentation. NEMB2016-6044
and cracking which have limited the adoption of vitrification in the past. Here
we present new physical, chemical, computational and biological data using
“nanowarming” to address this limitation. Specifically, we deploy 10 mg Fe/ Mingqiu Wang, Jered Haun, University of California, Irvine, Irvine,
ml biocompatible mesoporous silica-coated iron oxide magnetic nanoparti- CA, United States
cles (msIONPs) in a cryoprotective agent (VS55) which, when exposed to an
appropriate RF field, improves the uniformity and speed of rewarming from Targeted delivery of imaging or therapeutic agents holds tremendous po-
the vitrified state. The msIONPs are comprised of a 10 nm Fe O core and 25 tential to transform detection and treatment of diseases such as cancer
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nm mesoporous silica shell co-modified with PEG and trimethylsilane. As a and atherosclerosis. However, this potential has remained largely untapped
proof of principle human dermal fibroblasts (HDF) and porcine carotid arter- clinically because molecularly-targeted agents have failed to provide suffi-
ies (inner diameter of ~ 3 mm; wall thickness of ~1 mm and length: ~3-5 mm) cient delivery yield and/or specificity. Nanomaterial carriers offer numerous
were chosen as the systems of study. Protocols were optimized to step load advantages as a delivery platform, but targeted nanoparticle agent devel-
the nanoparticle impregnated VS55 into the HDF and artery systems with opment has focused primarily on generating specificity and evaluating ther-
negligible toxicity. The systems were then vitrified at roughly 10 °C/min. Micro modynamic behavior. But adhesion within the body is a dynamic process,
computed tomography was used as a quality control tool to demonstrate and thus we believe that a kinetic treatment will be far more powerful. In
both the loading and vitrification of the VS55 into the arteries. Rewarming previous work, we developed a framework to study multivalent nanopar-
was carried out in a low frequency (20KA/m, 360 KHz) RF field achieving ticle adhesion from a kinetic standpoint. This work also uncovered that
warming rates >> 55 °C/min (a critical rate to avoid devitrification of VS55) nanoparticle binding stability increases over time, which we captured by
or by less optimal rates (< 10 °C/min). Thermal measurements and modeling developing a time-dependent detachment rate with temporal (β) and mag-
verified the rates of freezing and heating in the systems tested. Further me- nitude (kD0) components. We have now developed a multi-scale dynamic
chanical modeling verified that the thermal stress remained below a 2 MPa simulation based on the Adhesive Dynamics simulation framework to study
yield stress of the tissue during nanowarming and no cracks were identified the dynamics and biophysics of multivalent nanoparticle binding to specific
in histology. The presence and washout of msIONPs in cells and luminal molecular targets. Using our Nano Adhesive Dynamics (NAD) simulations
structure of arteries was verified by TEM and sweep imaging with Fourier to model an antibody-conjugated nanoparticle binding to ICAM-1, we were
transform (SWIFT) MRI, respectively. The viability of HDFs and arteries 1 day able to replicate the time-dependent nanoparticle detachment behavior
after nanowarming were assessed by Hoechst-PI assays and Alamar Blue from experiments by tuning the bond mechanical properties, specifically the
and shown to remain ~ 85% of controls vs. ~ 30% of control when less opti- reactive compliance (γ) and bond spring constant (σ). We observed bonds
mal warming was used. In conclusion, this study provides the first evidence progressively increasing over time from one to as many as six depending on
that nanowarming can provide both the uniformity and speed necessary to the density of antibody or ICAM-1 employed. Furthermore, the time-course
successfully return cells and tissues from the vitrified state. by which bonds increased precisely matched the rate at which nanoparti-
cles adhesion was stabilizing. Interestingly, experimental results could be
Acknowledgements: Funding from NSF CBET 1336659, NIH R43HL123317, matched over a spectrum of γ-σ combinations, and these conditions were
NIH P41EB015894, the MN Futures grant (UM), and the Kuhrmeyer Chair to linked by similar mechanical work being performed on bonds (equal to the
JCB are gratefully acknowledged. We also thank the Visible Heart Lab (Iaiz- bond chemical energy) and the resultant average bond lifetime (~0.1 s). Since
zo) Charles Soule and Tinen Healy for access to porcine arteries and Connie we could not identify a unique solution, we performed optical tweezers
Chung for help with initial cell culture experiments. experiments at different force loading rates and found γ 0.27 nm. Using this
value, we found exquisite fits could be achieved for both the temporal (β)
and magnitude (kD0) components of our time-dependent detachment rate
across 9 different antibody and ICAM-1 density conditions using σ= 0.8 N/m.
2-7 Specifically, β ranged from 0.7-0.9, in comparison to 0.75 for experiments,
MODELING NANOPARTICLE TRANSPORT while kD0 deviated by less than 50% at all molecular density conditions.
Based on this work, we have correlated the nanoparticle-scale parameters
β and kD0 with individual bond information such as the average lifetime and
Bexar/Travis 9:30am - 11:00am equilibrium number; respectively. Our NAD simulations provide a unique tool
for analyzing multivalent nanoparticle adhesion data in a dynamic context
Session Organizer: Zhen Gu, University of North Carolina at Chapel and interpreting behavior at at the level of individual bonds. Most impor-
Hill and North Carolina State University, Raleigh, NC, United States tantly, the NAD simulations will be a powerful tool for designing targeted
nanoparticle agents and leveraging control over multivalency.
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9:30am Modeling cell mechanics from single cells to tissues
10:20am Modeling Intraarterial Cationic Nanoparticle Delivery