Research Focus

In biology there are numerous examples of systems which far exceed any man-made machine in terms of efficiency, precision, and complexity. We would like to be able to take advantage of the engineering that Nature has done for thousands of years and directly manipulate biological molecules. Our goals are to create nanoscale interfaces to biology to control biological processes. This requires not only exploiting the unique size and material dependent properties of nanoparticles but also understanding and engineering their interface to biology, which is a crucial part of their implementation in any biological application.

1. Charactering the Nanoparticle - Protein Interface

Nanoparticle-protein conjuagtes have been utilized in numerous applications such as sensing, self-assembly, and imaging. For these purposes, conjugation needs to be site-specific and should not perturb the structure and function of the protein. However, this is difficult to achieve as both nanoparticles and proteins are complex chemical systems, which can interact by numerous non-covalent interactions, or non-specific adsorption. Furthermore, characterization of the interface between the nanoparticle and protein is difficult and straightforward assays do not exist. Consequently the interface is poorly understood and remains to be one of the major barriers in employing nanoparticles in biological applications.

Our ultimate goal is to come up with general design rules for optimal conjugation of nanoparticles with a protein. Toward this end, we are studying the interface of nanoparticles with the proteins Ribonuclease S and Cytochrome c. We have determined how to label these proteins in a way that is site-specific. Current efforts are focused on studying the effect of labeling position, as well as nanoparticle ligand, size, and material on the biophysical properties of the protein.

2. Understanding nanoparticle interfaces to DNA

We are studying the biophysical and functional behavior of DNA covalently linked to gold nanoparticles. Covalent linking of DNA to nanoparticles often results in non-specific adsorption of the DNA to the nanoparticle surface. This is problematic as it can prevent the ability of the DNA to hybridize to a target. We are exploring ways to label DNA with nanoparticles in such a way that DNA function is retained. Effect of nanoparticle size, DNA sequence and composition, and nanoparticle surface functionalization are studied. In addition, we are evaluating tools such as quantitative gel electrophoresis to quantitatively assay the DNA conformation on the nanoparticle surface, and charge of the nanoparticle-DNA conjugate.

3. Using nanoparticles to trigger drug delivery

Spatial and temporal control over release of a drug is key for increasing drug efficacy. We are studying how to exploit the ability to heat magnetic nanoparticles with an external field to achieve this in thermosensitive liposomes. Liposomes are a well studied vehicle for drug delivery as they have a large internal aqueous space which can carry a payload. Upon heating these liposomes release their contents, so encapsulation of magnetic nanoparticles along with the drug of interest could enable externally triggered release.

We are studying how to encapsulate water soluble magnetic nanoparticles in liposomes at very high densities using the reverse-evaporation (REV) method. We have found that increasing the concentration of nanoparticles in liposomes can perturb the lipid phase diagram, and thus synthesis of large unilamellar vesicles encapsulating nanoparticles requires optimization of liposome synthesis parameters.

We are developing a means of orthogonally heating nanoparticles, so that magnetic fields of one frequency could be used to heat one type of nanoparticle, and another frequency could be used to heat another independently. We have devised a way to achieve this by exploiting the size and material dependence of magnetic field heating.

4. Laser excitation of gold nanorods

We are exploiting the unique material properties of gold nanorods to control biological processes. Ultrafast laser excitation can rapidly heat gold nanorods, which can be utilized to release biomolecules. Because the optical properties of gold nanorods are size and shape tunable, this permits tailoring the nanorod for strategically controlled release.

We are developing methods for ligand exchange so that functionalization with DNA and proteins is possible. We are studying the thermal properties of gold nanorods and how it is influenced by the surface coating ligand. Transient absorption spectroscopy is utilized to examine the thermal transport between gold nanorods and the solvent.

Publications

M.-E. Aubin-Tam, W. Hwang, K. Hamad-Schifferli, "Site-directed nanoparticle labeling of cytochrome c," 2008, in submission.

A. J. Schmidt,* J. D. Alper,* M. Chiesa, G. Chen, S. K. Das, K. Hamad-Schifferli, "Probing the gold nanorod-ligand-solvent interface by plasmonic absorption and thermal decay," Journal of Physical Chemistry C, 2008, in press.
*These authors contributed equally to the work.

A. Wijaya and K. Hamad-Schifferli, "Ligand customization and DNA functionalization of gold nanorods via roundtrip phase transfer ligand exchange," Langmuir, 2008, in press.

S. Park and K. Hamad-Schifferli, "Evaluation of hydrodynamic size and zeta-potential of surface-modified Au nanoparticle-DNA conjugates via Ferguson analysis," Journal of Physical Chemistry C, 2008, 112, 7611-7616.

K. A. Brown, S. Park, K. Hamad-Schifferli, "Nucleotide-Surface interactions in DNA modified Au-Nanoparticle Conjugates: Sequence Effects on Reactivity and Hybridization," Journal of Physical Chemistry C, 2008, 112, 7517-7521.

M.-E. Aubin-Tam, H. Zhou, and K. Hamad-Schifferli, "Structure of cytochrome c at the interface with magnetic CoFe2O4 nanoparticles," Soft Matter, 2008, 4, 554-559.

A. Wijaya and K. Hamad-Schifferli, "High density encapsulation of Fe3O4 nanoparticles in lipid vesicles," Langmuir, 2007, 23 (19) 9546-9550.

A. Wijaya, K. A. Brown, J.D. Alper, and K. Hamad-Schifferli, "Magnetic field heating study of Fe doped Au nanoparticles," Journal of Magnetism and Magnetic Materials, 2007, 309 (1) 15-19.

M.-E. Aubin-Tam and K. Hamad-Schifferli, "Gold nanoparticle-cytochrome c complexes: the effect of nanoparticle ligand charge on protein structure," Langmuir, 2005, 21 (26) 12080 - 12084.

M.-E. Aubin, D.G. Morales, K. Hamad-Schifferli, "Labeling Ribonuclease S with a 3nm Au nanoparticle by two-step assembly," Nano Letters, 2005, 5, 519-522.

S. Park, K. A. Brown, K. Hamad-Schifferli, "Changes in oligonucleotide conformation on nanoparticle surfaces by modification with mercaptohexanol," Nano Letters, 2004, 4, 1925-1929.

K. Hamad-Schifferli, J.J. Schwartz, A.T. Santos, S. Zhang, J.M. Jacobson, "Remote electronic control of DNA hybridization through inductive coupling to an attached metal nanocrystal antenna," Nature, 2002, 415, 152-155.

Review Papers

M.-E. Aubin-Tam, K. Hamad-Schifferli, "Structure and Function of Nanoparticle-Protein Conjugates," Biomedical Materials, special issue: Advanced methods and protocols for the biomedical sciences, 2008, invited contribution, in press.

K. Hamad-Schifferli, "Control of biomolecular activity by nanoparticle antennas," in BioMEMS and Biomedical Nanotechnology, vol II:Micro/Nano Technologies for Genomics and Proteomics, edited by Mihri Ozkan and Michael Heller (Kluwer, New York, 2006), invited contribution.

K. Hamad-Schifferli, in Encyclopedia of Nanoscience and Nanotechnology, edited by J. A. Schwarz, C. Contescu and K. Putyera (Marcel Dekker, New York, 2004), invited contribution.

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