Project Title: Characterization of Nanoparticle-Membrane Interactions

Project Duration: May 25 – August 1, 2015 (10 weeks), 40 hours per week.

Project Mentors

• Primary Faculty Mentor (Name, Affiliation, website and Email/Phone):
  • Eric Freeman, College of Engineering, http://freemangroup.wordpress.com, ecfreema@uga.edu

• Secondary Faculty Mentor (Name, Affiliation, website and Email/Phone):
  • Xianqiao Wang, College of Engineering, http://xqwang.engr.uga.edu/index.htm, xqwang@uga.edu
• Graduate Student/PostDoc mentors (Name, Affiliation and Email/Phone):
  • Kengelle Chukwurah, College of Engineering (Freeman), chukwurah@yahoo.com
  • Khushboo Brahmbatt, College of Engineering (Freeman), khushb89@uga.edu

Project Description:

As nanotechnology-based approaches in engineering continue to increase in popularity, research must be conducted to assess the impact of environmentally-distributed nanoparticles with biological systems. As the field of nanotechnology is relatively new, there is currently a lack of information involving the interactions of the nanoparticles in an aqueous, cellular environment [1]. Nanoparticles may prove beneficial as therapeutic agents for cancer treatments and imaging [2-5] or for modifying the properties of cellular membranes and liposomes [6, 7]; however they may also play a role in disrupting healthy membrane function [8-10].

These interactions may be characterized through computational simulation and through experimental study. Coarse-grained molecular dynamics simulations allow for the assessment of nanoparticle interactions with the cellular membranes; such as dissolving in the membrane hydrocarbon interior dependent on the surface treatment of the nanoparticles and penetration through the membrane through externally applied forces. These predictions may be validated experimentally through a “bottoms-up” approach to synthetic biology [11], creating model membranes that mimic the cellular membrane and provide a controlled environment for repeatable characterization of their interactions with the environment. In this work, experimentally observed phenomena involving membrane-nanoparticle interactions will be examined through computational methods, providing insight into the underlying nature of the experimental observations.

REU Student Role and Responsibility:

Coarse-Grained Molecular Dynamics Simulations: Existing nanoparticle-membrane simulations will be reviewed and methods for experimentally validating these predictions will be generated by the student with input from the advisors.

Substrate Manufacture and Design: The student will design a suitable microfluidic chamber or substrate for observing the interactions between model membranes and the nanoparticles. The molds will be fabricated in the Driftmier machine shop, and the student will create the substrates through either PDMS or urethane rubber.

Experimental Assessment of Membrane-Nanoparticle Interactions: Liposomes or model membranes will be created either through sonication, droplet-interface bilayers, extrusion, or electroformation. Solutions containing the nanoparticles of interest will be injected into the liposome-containing substrates and their interactions with the contained liposomes will be quantified through microscopy and voltage-clamp electrophysiology. The outcomes will be compared to the computational predictions and discussed.

Expected Outcome for REU student: The student’s project will contribute to the development of a manuscript intended for the Journal of Physical Chemistry, in addition to a conference paper focused primarily on the student’s contributions. The student will be listed as a co-author on the journal publication and primary author on the conference paper. Outcomes of the research include a repeatable methodology for forming large, stable liposomes and applying this methodology towards studying the interactions of lipid bilayer membranes with their surrounding environment.

REFERENCES

1. Moore, M., Do nanoparticles present ecotoxicological risks for the health of the aquatic environment? Environment International, 2006. 32(8): p. 967-976.
2. Béalle, G.l., et al., Ultra magnetic liposomes for MR imaging, targeting, and hyperthermia. Langmuir, 2012. 28(32): p. 11834-11842.
3. Habault, D., et al., Droplet microfluidics to prepare magnetic polymer vesicles and to confine the heat in magnetic hyperthermia. Magnetics, IEEE Transactions on, 2013. 49(1): p. 182-190.
4. Pankhurst, Q.A., et al., Applications of magnetic nanoparticles in biomedicine. Journal of physics D: Applied physics, 2003. 36(13): p. R167.
5. Wu, G., et al., Remotely triggered liposome release by near-infrared light absorption via hollow gold nanoshells. Journal of the American Chemical Society, 2008. 130(26): p. 8175-8177.
6. Schulz, M., A. Olubummo, and W.H. Binder, Beyond the lipid-bilayer: interaction of polymers and nanoparticles with membranes. Soft Matter, 2012. 8(18): p. 4849-4864.
7. Mashaghi, S., et al., Lipid nanotechnology. International journal of molecular sciences, 2013. 14(2): p. 4242-4282.
8. Santos, S.M., et al., Interaction of fullerene nanoparticles with biomembranes: from the partition in lipid membranes to effects on mitochondrial bioenergetics. Toxicological Sciences, 2013: p. kft327.
9. Corredor, C., et al., Disruption of model cell membranes by carbon nanotubes. Carbon, 2013. 60: p. 67-75.
10. Baoukina, S., L. Monticelli, and D.P. Tieleman, Interaction of Pristine and Functionalized Carbon Nanotubes with Lipid Membranes. The Journal of Physical Chemistry B, 2013. 117(40): p. 12113-12123.
11. Zhang, Y., W.C. Ruder, and P.R. LeDuc, Artificial cells: building bioinspired systems using small-scale biology. TRENDS in Biotechnology, 2008. 26(1): p. 14-20.

Gay REU Poster