This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Salicylate is the active metabolite of aspirin and a member of the popular non-steroidal anti-inflammatory drugs (NSAIDs) used to treat fever, pain and arthritis. However, it is known to cause ulcers, which could be explained by the ability of the molecule to disrupt the phospholipid layer covering the gastric mucosa. Because mechanical properties of a lipid membrane can be altered by minor changes in the chemistry of the proteins or lipids that compose the membrane, and because electrostatics is the most dominant force at the nanoscale, it is believed that more detailed measurements of salicylate-lipid interactions will provide insights into these fundamental biological processes. Surface-Enhanced Raman Scattering (SERS) response of gold nanoshells, which are tunable optical nanoparticles consisting of a dielectric (silica) core and a thin metallic (gold) shell, can be a very useful tool to probe salicylate membrane interactions. The optical resonance of nanoshells gives rise to an intense optical field at the surface of the nanoparticle. The high optical intensities at the nanoshell surface can be used to enhance the chemical spectroscopic signal of salicylate, a Raman-active molecule, which when embedded in a lipid membrane on the surface of the nanoshell should yield a strong SERS signal. Thus, SERS will be useful to probe lipid membrane properties and monitor the insertion of salicylic acid molecules into the lipid membrane. SERS measurements of inserted salicylate hinges on successful liposome- encapsulation of nanoshells. This requires extensive microscopic characterization of the lipid-nanoshell interacting system. CryoEM measurements can provide evidence of liposome-encapsulation of nanoshells and can help establish the thickness of the lipid membrane formed around the nanoshells. Therefore, cryoEM imaging is essential to the progress of this project. Imaging of the prepared liposome-nanoshell samples will be conducted at the cryoEM facility at NCMI. Results from our studies will relate our continuum micromechanical measurements to molecular interactions. In addition to studying the effect salicylate has on membrane dynamics, nanoshell-encapsulated liposomes may provide a vehicle for intracellular uptake of nanoshells which can be useful for drug delivery.
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