Using a recently described self-assembly process (Bayburt, T. H.; Grinkova, Y. V.; Sligar, S. G. Nano Letters 2002, 2, 853-856), we prepared soluble monodisperse discoidal lipid/protein particles with controlled size and composition, termed Nanodiscs, in which the fragment of dipalmitoylphosphatidylcholine (DPPC) bilayer is surrounded by a helical protein belt. We have customized the size of these particles by changing the length of the amphipathic helical part of this belt, termed membrane scaffold protein (MSP). Herein we describe the design of extended and truncated MSPs, the optimization of self-assembly for each of these proteins, and the structure and composition of the resulting Nanodiscs. We show that the length of the protein helix surrounding the lipid part of a Nanodisc determines the particle diameter, as measured by HPLC and small-angle X-ray scattering (SAXS). Using different scaffold proteins, we obtained Nanodiscs with the average size from 9.5 to 12.8 nm with a very narrow size distribution (+/-3%). Functionalization of the N-terminus of the scaffold protein does not perturb their ability to form homogeneous discoidal structures. Detailed analysis of the solution scattering confirms the presence of a lipid bilayer of 5.5 nm thickness in Nanodiscs of different sizes. The results of this study provide an important structural characterization of self-assembled phospholipid bilayers and establish a framework for the design of soluble amphiphilic nanoparticles of controlled size.

A study aimed at understanding the factors that control the optical properties of DNA-linked gold nanoparticle aggregates containing oligonucleotide linkers of varying length (24−72 base pairs) is described. In this system, ∼15 nm diameter Au particles modified with (alkanethiol)-12 base oligomers are hybridized to a series of oligonucleotide linkers ranging from 24 to 72 base pairs (∼80−240 Å) in length. Aggregated at room temperature, the various macroscopic nanoparticle assemblies have plasmon frequency changes that are inversely dependent on the oligonucleotide linker length. Upon annealing at temperatures close to the melting temperature of the DNA, the optical properties of the DNA-linked assemblies containing the longer linkers (48 and 72 base pairs) red-shift until they are similar to the assemblies containing the shorter linkers (24 base pairs). The pre- and postannealed DNA-linked assemblies were characterized by sedimentation rate, transmission electron microscopy, dynamic light scattering, and UV−vis spectroscopy which show that the oligonucleotide linker length kinetically controls the size of the aggregates that are formed under the preannealed conditions, thereby controlling the optical properties. Through the use of small-angle X-ray scattering and electrodynamic modeling in conjunction with the techniques mentioned above, we have determined that the temperature-dependent optical changes observed upon annealing of the aggregates containing the longer oligonucleotides (48 and 72 base pairs) can be attributed to aggregate growth through an “Ostwald ripening” mechanism (where larger aggregates grow at the expense of smaller aggregates). This type of aggregate growth leads to the red-shift in plasmon frequency observed for the aggregates. Significantly, these experiments provide evidence that the optical properties of these DNA-linked nanoparticle assemblies are governed by aggregate size, regardless of oligonucleotide linker length, which has important implications for the development of colorimetric detection methods based on these nanoparticle materials.

Electrodynamic simulations of gold nanoparticle spectra were used to investigate the sensitivity of localized surface plasmon band position to the refractive index, n, of the medium for nanoparticles of various shapes and nanoshells of various structures. Among single-component nanoparticles less than 130 nm in size, sensitivities of dipole resonance positions to bulk refractive index are found to depend only upon the wavelength of the resonance and the dielectric properties of the metal and the medium. Among particle plasmons that peak in the frequency range where the real part of the metal dielectric function varies linearly with wavelength and the imaginary part is small and slowly varying, the sensitivity of the peak wavelength, lambda, to refractive index, n, is found to be a linearly increasing function of lambda, regardless of the structural features of the particle that determine lambda. Quasistatic theory is used to derive an analytical expression for the refractive index sensitivity of small particle plasmon peaks. Through this analysis, the dependence of sensitivity on band position is found to be determined by the wavelength dependence of the real part, epsilon', of the particle dielectric function, and the sensitivity results are found to extend to all particles with resonance conditions of the form, epsilon' = -2chin(2), where chi is a function of geometric parameters and other constants. The sensitivity results observed using accurate computational methods for dipolar plasmon bands of gold nanodisks, nanorods, and hollow nanoshells extend, therefore, to particles of other shapes (such as hexagonal and chopped tetrahedral), composed of other metals, and to higher-order modes. The bulk refractive index sensitivity yielded by the theory serves as an upper bound to sensitivities of nanoparticles on dielectric substrates and sensitivities of nanoparticles to local refractive index changes, such as those associated with biomolecule sensing.

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