Calcium-triggered fusion of lipid membranes is enabled by amphiphilic nanoparticles.

Lipid membrane fusion is an essential process for a number of critical biological functions. The overall process is thermodynamically favorable but faces multiple kinetic barriers along the way. Inspired by nature's engineered proteins such as SNAP receptor [soluble N-ethylmale-imide-sensitive factor-attachment protein receptor (SNARE)] complexes or viral fusogenic proteins that actively promote the development of membrane proximity, nucleation of a stalk, and triggered expansion of the fusion pore, here we introduce a synthetic fusogen that can modulate membrane fusion and equivalently prime lipid membranes for calcium-triggered fusion. Our fusogen consists of a gold nanoparticle functionalized with an amphiphilic monolayer of alkanethiol ligands that had previously been shown to fuse with lipid bilayers. While previous efforts to develop synthetic fusogens have only replicated the initial steps of the fusion cascade, we use molecular simulations and complementary experimental techniques to demonstrate that these nanoparticles can induce the formation of a lipid stalk and also drive its expansion into a fusion pore upon the addition of excess calcium. These results have important implications in general understanding of stimuli-triggered fusion and the development of synthetic fusogens for biomedical applications.

Effect of surface properties on nanoparticle-cell interactions.

The interaction of nanomaterials with cells and lipid bilayers is critical in many applications such as phototherapy, imaging, and drug/gene delivery. These applications require a firm control over nanoparticle-cell interactions, which are mainly dictated by surface properties of nanoparticles. This critical Review presents an understanding of how synthetic and natural chemical moieties on the nanoparticle surface (in addition to nanoparticle shape and size) impact their interaction with lipid bilayers and cells. Challenges for undertaking a systematic study to elucidate nanoparticle-cell interactions are also discussed.

Supramolecular nanostamping: using DNA as movable type.

Here we present a novel printing technique (that we call supramolecular nanostamping), based on the replication of single-stranded DNA features through a hybridization-contact-dehybridization cycle. On a surface containing features each made of single-stranded DNA molecules of known sequence, the complementary DNA molecules are hybridized, spontaneously assembling onto the original pattern due to sequence-specific interactions. These complementary DNA strands, on the end that is assembled far from the original surface, are 5' modified with chemical groups ("sticky ends") that can form bonds with a target surface that is brought into contact. Heating induces dehybridization between DNA strands, leaving the original pattern on the original surface and the copied pattern on the secondary substrate, and thus stamping (see Figure 1). Molecular recognition provides the unique and disruptive ability of transferring large amounts of information in a single printing cycle, that is the simultaneous stamping of spatial information (i.e., the patterns) and of chemical information (i.e., the features' DNA sequence--their chemical composition). This method combines high resolution (<40 nm) with the advantage of an exponential increase in the number of masters; in fact, any printed substrate can be reused as a master. Patterns fabricated via very different lithographic techniques can be replicated.