Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells

HIV represents a persistent infection which negatively alters the immune system. New tools to reinvigorate different immune cell populations to impact HIV are needed. Herein, a novel nanotool for the specific enhancement of the natural killer (NK) immune response towards HIV-infected T-cells has been developed. Bispecific Au nanoparticles (BiAb-AuNPs), dually conjugated with IgG anti-HIVgp120 and IgG anti-human CD16 antibodies, were generated by a new controlled, linker-free and cooperative conjugation method promoting the ordered distribution and segregation of antibodies in domains. The cooperatively-adsorbed antibodies fully retained the capabilities to recognize their cognate antigen and were able to significantly enhance cell-to-cell contact between HIV-expressing cells and NK cells. As a consequence, the BiAb-AuNPs triggered a potent cytotoxic response against HIV-infected cells in blood and human tonsil explants. Remarkably, the BiAb-AuNPs were able to significantly reduce latent HIV infection after viral reactivation in a primary cell model of HIV latency. This novel molecularly-targeted strategy using a bispecific nanotool to enhance the immune system represents a new approximation with potential applications beyond HIV.This study was supported by the Spanish Secretariat of Science and Innovation and FEDER funds (grants SAF2015-67334-R and RTI2018-101082-B-I00 [MINECO/FEDER]), American National Institutes of Health (grant R21AI118411 to M.B), an unrestricted research grant from Bristol-Myers Squibb S.A.U (PfC-2015-AI424-564) to M.B, the Spanish “Ministerio de Economía y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI17/01470) to M.G and the Spanish “Ministerio de Economía y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI14/01058) to J.G.P, a research grant from Gilead Sciences (GLD17-00204 and GLD19-00084) to M.B, GeSIDA and the Spanish AIDS network “Red Temática Cooperativa de Investigación en SIDA” (RD16/0025/0007). The Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179) to M.B and J.G.P (CPII15/00014). The “Pla estratègic de recerca i innovació en salut” (PERIS), from the Catalan Government to M.G. The Spanish Secretariat of Science and Innovation Ph.D. fellowship to A.A-G (BES-2016-076382), AGAUR-FI-B-00582 Ph.D. fellowship from the Catalan Government to O.BL, and PIF-UAB Ph.D. fellowship from Universitat Autònoma de Barcelona to R.SL.Peer reviewe

Thermodynamic and Structural Phase Behavior of Colloidal and Nanoparticle Systems.

We design and implement a scalable hard particle Monte Carlo simulation toolkit (HPMC), and release it open source. Common thermodynamic ensembles can be run in two dimensional or three dimensional triclinic boxes. We developed an efficient scheme for hard particle pressure measurement based on volume perturbation. We demonstrate the effectiveness of low order virial coefficients in describing the compressibility factor of fluids of hard polyhedra. The second virial coefficient is obtained analytically from particle asphericity and can be used to define an effective sphere with similar low-density behavior. Higher-order virial coefficients --- efficiently calculated with Mayer Sampling Monte Carlo --- are used to define an exponential approximant that exhibits the best known semi-analytic characterization of hard polyhedron fluid state functions. We present a general method for the exact calculation of convex polyhedron diffraction form factors that is more easily applied to common shape data structures than the techniques typically presented in literature. A proof of concept user interface illustrates how a researcher might investigate the role of particle form factor in the diffraction patterns of different particles in known structures. We present a square-triangle dodecagonal quasicrystal (DQC) in a binary mixture of nanocrystals (NCs). We demonstrate how the decoration of the square and triangle tiles naturally gives rise to partial matching rules via symmetry breaking in layers perpendicular to the dodecagonal axis. We analyze the geometry of the experimental tiling and, following the ``cut and project'' theory, lift the square and triangle tiling pattern to four dimensional space to perform phason analysis historically applied only in simulation and atomic systems. Hard particle models are unsuccessful at explaining the stability of the binary nanoparticle super lattice. However, with a simple isotropic soft particle model, we are able to demonstrate seeded growth of the experimental structure in simulation. These simulations indicate that the most important stabilizing properties of the short range structure are the size ratio of the particles and an A--B particle attraction.PhDMaterials Science and EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/120906/1/eirrgang_1.pd