Membrane Fluctuation Model for Understanding the Effect of Receptor Nanoclustering on the Activation of Natural Killer Cells through Biomechanical Feedback.

We investigated the role of ligand clustering and density in the activation of natural killer (NK) cells. To that end, we designed reductionist arrays of nanopatterned ligands arranged with different cluster geometries and densities and probed their effects on NK cell activation. We used these arrays as an artificial microenvironment for the stimulation of NK cells and studied the effect of the array geometry on the NK cell immune response. We found that ligand density significantly regulated NK cell activation while ligand clustering had an impact only at a specific density threshold. We also rationalized these findings by introducing a theoretical membrane fluctuation model that considers biomechanical feedback between ligand-receptor bonds and the cell membrane. These findings provide important insight into NK cell mechanobiology, which is fundamentally important and essential for designing immunotherapeutic strategies targeting cancer.

A Novel Approach for Colloidal Lithography: From Dry Particle Assembly to High-Throughput Nanofabrication.

We introduce a novel approach for colloidal lithography based on the dry particle assembly into a dense monolayer on an elastomer, followed by mechanical transfer to a substrate of any material and curvature. This method can be implemented either manually or automatically and it produces large area patterns with the quality obtained by the state-of-the-art colloidal lithography at a very high throughput. We first demonstrated the fabrication of nanopatterns with a periodicity ranging between 200 nm and 2 µm. We then demonstrated two nanotechnological applications of this approach. The first one is antireflective structures, fabricated on silicon and sapphire, with different geometries including arrays of bumps and holes and adjusted for different spectral ranges. The second one is smart 3D nanostructures for mechanostimulation of T cells that are used for their effective proliferation, with potential application in cancer immunotherapy. This new approach unleashes the potential of bottom-up nanofabrication and paves the way for nanoscale devices and systems in numerous applications.

Multifunctional Nanoscale Platform for the Study of T Cell Receptor Segregation.

T cells respond not only to biochemical stimuli transmitted through their activating, costimulatory, and inhibitory receptors but also to biophysical aspects of their environment, including the receptors' spatial arrangement. While these receptors form nanoclusters that can either colocalize or segregate, the roles of these colocalization and segregation remain unclear. Deciphering these roles requires a nanoscale platform with independent and simultaneous spatial control of multiple types of receptors. Herein, using a straightforward and modular fabrication process, we engineered a tunable nanoscale chip used as a platform for T cell stimulation, allowing spatial control over the clustering and segregation of activating, costimulatory, and inhibitory receptors. Using this platform, we showed that, upon blocked inhibition, cells became sensitive to changes in the nanoscale ligand configuration. The nanofabrication methodology described here opens a pathway to numerous studies, which will produce an important insight into the molecular mechanism of T cell activation. This insight is essential for the fundamental understanding of our immune system as well as for the rational design of future immunotherapies.

Nanocomposite coatings for the prevention of surface contamination by coronavirus.

The current Covid-19 pandemic has a profound impact on all aspects of our lives. Aside from contagion by aerosols, the presence of the SARS-CoV-2 is ubiquitous on surfaces that millions of people handle daily. Therefore, controlling this pandemic involves the reduction of potential infections via contaminated surfaces. We developed antiviral surfaces by preparing suspensions of copper and cupric oxide nanoparticles in two different polymer matrices, poly(methyl methacrylate) and polyepoxide. For total copper contents as low as 5%, the composite material showed remarkable antiviral properties against the HCoV-OC43 human coronavirus and against a model lentivirus and proved well-resistant to accelerated aging conditions. Importantly, we showed that the Cu/CuO mixture showed optimal performances. This product can be implemented to produce a simple and inexpensive coating with long-term antiviral properties and will open the way to developing surface coatings against a broad spectrum of pathogens including SARS-CoV-2.

Surface plasticizing of chalcogenide glasses: a route for direct nanoimprint with multifunctional antireflective and highly hydrophobic structures.

Chalcogenide glasses are attractive materials for optical applications. However, these applications often require pattering of the surface with functional micro-/ nanostructures, which is challenging by traditional microfabrication. Here, we present a novel, robust, and scalable approach for the direct patterning of chalcogenide glasses, based on soft imprinting of a solvent-plasticized glass layer formed on the glass surface. We established a methodology for surfaces plasticizing, through tuning of its glass transition temperature by process conditions, without compromising on the chemical composition, structure, and optical properties of the plasticized layer. This control over the glass transition temperature allowed to imprint the surface of chalcogenide glass with features sized down to 20 nm, and achieve an unprecedented combination of full pattern transfer and complete maintenance of the shape of the imprinted substrate. We demonstrated two applications of our patterning approach: a diffraction grating, and a multifunctional pattern with both antireflective and highly hydrophobic water-repellent functionalities - a combination that has never been demonstrated for chalcogenide glasses. This work opens a new route for the nanofabrication of optical devices based on chalcogenide glasses and paves the way to numerous future applications for these important optical materials.

Soft thermal nanoimprint with a 10 nm feature size.

Nanoimprinting with rigid molds offers almost unlimited pattern resolution, but it suffers from high sensitivity to defects, and is limited to pattering flat surfaces. These limitations can be addressed by nanoimprinting with soft molds. However, soft molds have been used so far with UV resists, and could not achieve a resolution and minimal feature size comparable to those of rigid molds. Here, we explore the miniaturization edge of soft nanoimprint molds, and demonstrate their compatibility with thermal imprint resists. To that end, we produced a pattern with 10 nm critical dimensions, using electron beam lithography, and used it to replicate nanoimprint molds by direct casting of an elastomer onto the patterned resist. We showed that the produced pattern can be faithfully transferred from the mold by thermal nanoimprinting. In addition, we showed that similar nanoimprint molds can also be produced by double replication, which includes nanoimprinting of a thermal resist with an ultrahigh resolution rigid mold, and replication of a soft mold from the imprint pattern. We also demonstrated our novel nanoimprinting approach in two unconventional applications: nanopatterning of a thermal resist on a lens surface, and direct nanoimprinting of chalcogenide glass. Our novel nanoimprint approach pushes the envelope of standard nanofabrication, and demonstrates its potential for numerous applications impossible up to now.