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Arek M Engstrom,1 Ryan A Faase,2 Grant W Marquart,3 Joe E Baio,2 Marilyn R Mackiewicz,3 Stacey L Harper1,2,4 1Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, United States; 2School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR, United States; 3Department of Chemistry, Portland State University, Portland, OR, United States; 4Oregon Nanoscience and Microtechnologies Institute, Corvallis, OR, United StatesCorrespondence: Stacey L Harper Email Stacey.Harper@oregonstate.eduIntroduction: Humans are intentionally exposed to gold nanoparticles (AuNPs) where they are used in variety of biomedical applications as imaging and drug delivery agents as well as diagnostic and therapeutic agents currently in clinic and in a variety of upcoming clinical trials. Consequently, it is critical that we gain a better understanding of how physiochemical properties such as size, shape, and surface chemistry drive cellular uptake and AuNP toxicity in vivo. Understanding and being able to manipulate these physiochemical properties will allow for the production of safer and more efficacious use of AuNPs in biomedical applications.Methods and Materials: Here, AuNPs of three sizes, 5 nm, 10 nm, and 20 nm, were coated with a lipid bilayer composed of sodium oleate, hydrogenated phosphatidylcholine, and hexanethiol. To understand how the physical features of AuNPs influence uptake through cellular membranes, sum frequency generation (SFG) was utilized to assess the interactions of the AuNPs with a biomimetic lipid monolayer composed of a deuterated phospholipid 1.2-dipalmitoyl-d62-sn-glycero-3-phosphocholine (dDPPC).Results and Discussion: SFG measurements showed that 5 nm and 10 nm AuNPs are able to phase into the lipid monolayer with very little energetic cost, whereas, the 20 nm AuNPs warped the membrane conforming it to the curvature of hybrid lipid-coated AuNPs. Toxicity of the AuNPs were assessed i