Phase Behavior and Selectivity of DNA-Linked Nanoparticle Assemblies

Abstract

We propose a model that can account for the experimentally observed phase behavior of DNAnanoparticle assemblies (R. Jin et al., JACS 125, 1643; T. A. Taton et al., Science 289, 1757Science 289, (2000). The binding of DNA-coated nano-particles by dissolved DNA linker can be described by exploiting an analogy with quantum particles obeying fractional statistics. In accordance with experimental findings, we predict that the phase-separation temperature of the nano-colloids increases with the DNA coverage of the colloidal surface. Upon the addition of salt, the demixing temperature increases logarithmically with the salt concentration. Our analysis suggests an experimental strategy to map microscopic DNA sequences onto the macroscopic phase behavior of the DNA-nanoparticle solutions. Such an approach should enhance the efficiency of methods to detect (single) mutations in specific DNA sequences. PACS numbers:Colloidal particles that can be selectively linked by specific sequences single-stranded DNA, represent an entirely novel class of complex liquids. With these particles, it becomes feasible to "design" multicomponent mixtures, where the attractive interaction between every pair of species can be controlled independently.During the past few years, the unique molecular recognition properties of DNA have been exploited to create self-assembled nano-structures and nano-devices with a remarkable degree of control (see e.g. Ref.[1]). Self-assembled nanostructures based on DNA have also been utilized to detect specific DNA sequences [2,3,4,5]. In nanoparticle-based DNA detection systems, single-stranded DNA (ssDNA) "probe" molecules are chemisorbed onto the surface of gold nanoparticles (Fig. 1). These probe ssDNA's can specifically bind to a dissolved "target" ssDNA and thus detect its presence with high sensitivity and selectivity: at high enough concentration, the target ssDNA strands induces a sharp demixing transition [6] that leads to aggregation of the nanoparticles coated with the complementary "probe" strands. These aggregates can be easily detected by optical means.The sensitivity of the nanoparticle-based DNA detection method is some two orders of magnitude higher than that of the corresponding fluorophore-based DNA-array scheme [3]. But, in addition, the method can be used to distinguish different DNA sequences that differ from each other by only a single base. The reason is that a single mismatch in the DNA sequence results in a significant change in the DNA-colloid demixing temperature. The fluorophore-based systems lack this level of selectivity [3].In a recent paper, Jin et al. [4] have analyzed the dependence of the dissolution temperature (see note [6]) of DNA-linked nanoparticles on the DNA coverage density, the particle size, and the salt concentration. In the experiments [3,4] short DNA molecules (∼ 20-base oligonucleotides) and small gold colloids (∼ 10 − 50 nm) were used. The principal experimental findings are the following: (i) The higher the ssDNA coverage density on the surface of colloi...

Surface and bulk dissolution properties, and selectivity of DNA-linked nanoparticle assemblies

“…Part of our results were published in the recent paper. 36 Our results are in qualitative agreement with the experimental findings of Ref. 3.…”

“…36 we proposed a possible scenario to distinguish a specific target ssDNA AЈBЈ by monitoring the composition of phases in a three-component system of A, B, and C colloids. We noticed very generally that if the target AЈBЈ binds to AB ͑AЈBЈ / AB͒ and AC ͑AЈBЈ / AC͒ with slightly different affinities ͑i.e., AB and AC have similar sequences which are only different by a mismatch, either a single base or multiple base͒, one can distinguish the sequence of the target by monitoring the composition difference of B and C colloids in a dense ͑or dilute͒ phase.…”

Disorder in DNA-Linked Gold Nanoparticle Assemblies

“…The interaction potential between these colloids are tunable and controllable, which makes these multicomponent complex fluids particularly suitable for studying the link between the interaction potential and phase behavior [6,7]. Similar colloidal phase transitions have also been used to detect the protein interactions at membrane surfaces [8].…”

“…The assembly melting temperature is dependent upon parameters such as particle size, DNA composition, and electrolyte concentrations [1,2]. Recent theory has sought to explain these observations [6,23,24]. More study is necessary to fully understand the underlying mechanisms affecting the phase behavior of this system.…”

“…Gold-attached DNA clusters were prepared using linkers that ranged from 24 to 16 bases in length. The linker concentration was adjusted to be oversaturated so the melting temperature does not depend on linker concentration [6,25]. Typical 10 nm gold and DNA linker concentrations were ~4×10 17 particles/l and 7×10 −6 M, respectively.…”