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Photonic crystals—a class of materials whose optical properties derive from their structure in addition to their composition—can be created by self-assembling particles whose sizes are comparable to the wavelengths of visible light. Proof-of-principle studies have shown that DNA can be used to guide the self-assembly of micrometer-sized colloidal particles into fully programmable crystal structures with photonic properties in the visible spectrum. However, the extremely temperature-sensitive kinetics of micrometer-sized DNA-functionalized particles has frustrated attempts to grow large, monodisperse crystals that are required for photonic metamaterial applications. Here we describe a robust two-step protocol for self-assembling single-domain crystals that contain millions of optical-scale DNA-functionalized particles: Monodisperse crystals are initially assembled in monodisperse droplets made by microfluidics, after which they are grown to macroscopic dimensions via seeded diffusion-limited growth. We demonstrate the generality of our approach by assembling different macroscopic single-domain photonic crystals with metamaterial properties, like structural coloration, that depend on the underlying crystal structure. By circumventing the fundamental kinetic traps intrinsic to crystallization of optical-scale DNA-coated colloids, we eliminate a key barrier to engineering photonic devices from DNA-programmed materials. DNA-programmed colloidal assembly of macroscopic crystals for photonic applications remains elusive. Here, the authors use insights from studies of nucleation and seeded growth to develop a two-step method for assembling macroscopic photonic crystals.

DNA-coated colloids can self-assemble into an incredible diversity of crystal structures, but their applications have been limited by poor understanding and control over the crystallization dynamics. To address this challenge, we use microfluidics to quantify the kinetics of DNA-programmed self-assembly along the entire crystallization pathway, from thermally activated nucleation through reaction-limited and diffusion-limited phases of crystal growth. Our detailed measurements of the temperature and concentration dependence of the kinetics at all stages of crystallization provide a stringent test of classical theories of nucleation and growth. After accounting for the finite rolling and sliding rates of micrometer-sized DNA-coated colloids, we show that modified versions of these classical theories predict the absolute nucleation and growth rates with quantitative accuracy. We conclude by applying our model to design and demonstrate protocols for assembling large single crystals with pronounced structural coloration, an essential step in creating next-generation optical metamaterials from colloids.

DNA-coated colloids are in a constantly advancing field of programmable self-assembly that promises to allow researchers to assemble structures out of components that are neither on the macroscopic scale, nor on the atomic scale: a region that is surprisingly difficult to work in. Colloidal crystals have been one of the first structures people researching these particles have tried to assemble. This is no surprise as these particles have been described as \"programmable atom equivalents\" and crystallization is one of the defining phenomena of the atomic world. However, colloidal crystals have an important distinction in that they can be made up of particles of a similar size to light which allows researchers to envision self-assembling materials that have arbitrary photonic properties by exploiting the incredible flexibility a DNA-based system provides. In this work we studied the self-assembly of colloidal crystals made from these particles and arrived at conclusions about how they nucleate and grow and what has been missing in prior attempts to assemble large crystals.We perform a variety studies of the self-assembly of DNA-coated particles into colloidal crystals and find that a modified classical nucleation theory that includes the rate at which loosely bound particles on a pre-critical nuclei surface roll into a crystalline binding spot quantitatively and accurately describes the nucleation rate of these crystals in a range of conditions. We make an emulsion of monodisperse nanoliter scale droplets filled with DNA-coated particles and precisely measure the nucleation rate of crystals within the droplets as a function of temperature and particle concentration. We also measure the rate of growth and the equilibrium concentration of the crystal phase by measuring the gas density of each droplet over the course of the experiment. We then fit the equilibrium concentration with respect to system temperature to an exponential which we use to redefine the droplet temperature and concentration as a degree of supersaturation. We find the nucleation rate increases with the supersaturation in accordance with classical nucleation theory, and with a prefactor that scales linearly with particle concentration which is an unexpected deviation from current theory and is a unique feature of DNA-coated colloids which mediate their interaction through several transient DNA bonds. This leads to a timescale in which particles that impinge on a crystal surface must diffuse along that surface via the constant severing and reforming of DNA bonds until the particle is in a crystalline position. After this initial stage of nucleation and growth we find that the crystal grows in a deterministic and diffusion limited way.We then show that particles in nanoliter droplets are excellent incubators for single crystals with sizes that can be precisely defined by changing the number of particles within the droplets, allowing for near-digital control of the final crystal size. We find that once a crystal begins growing in a droplet that the nucleation rate within the gas phase of the droplet decreases in accordance to our nucleation and growth model. We define a parameter which represents the timescale it takes for a growing crystal to sufficiently deplete the gas phase enough to suppress further nucleation which leads to a way to compare the rates of crystal nucleation and crystal growth in order to engineer a system that preferentially self-assembles single crystals. With this advanced understanding of all phases of the nucleation and growth of DNA-coated particles, we develop a protocol to more easily self-assemble single crystals which may find use in fields such as optical photonics and medicine. Namely, we find that by using a slow staircase temperature ramp protocol as opposed to a single isothermal step, we can much more easily self-assemble droplets with single crystals without having to worry about the extreme precision necessary to grow single crystals normally and we demonstrate that this protocol is actually near optimal given the constraints of our system.Despite the promise of droplets in making monodisperse crystals, we find that this system is fundamentally unable to grow a high yield single crystals beyond a certain size as the region of temperature where the growth rate and the nucleation rate are comparable is too narrow when the droplets are large, and practical solutions like decreasing the temperature ramp rate or increasing the droplet particle fraction are not feasible to the degree they would be required. We get around these issues by developing a novel two-step protocol that involves in the first step using small droplets to make tiny crystals to act as seeds for further growth. A small number of these seeds are then removed from the emulsion and added to a bulk system of new particles that has a melting temperature a couple degrees below that of the seeds, allowing the seed crystals to be stable while the bulk is in its gas phase. We slowly cool this system down until the seeds begin to grow. This occurs at a supersaturation where further nucleation from the bulk is incredibly unlikely, thus preserving the number of crystals in the system from start to finish, removing the usual difficulties of assembling monodisperse single crystals in the bulk.We find that the growth of these crystals are diffusion limited and fully predictable as long as the seeds are not within a few crystal diameters of each other as they will begin to compete for the particles in the gas phase. This second growth stage is theoretically unbounded, with our method being able to produce the largest DNA-coated crystal to date at 0.3 mm in length containing 30,000,000 particles and being visible to the naked eye.We finally demonstrate that these crystals have photonic properties by imaging them in reflection and cross polarized transmission. We find that in reflection, crystals made from different sized particles tend to shine different colors. And in transmission we find a variety of vibrant colors that depend on the orientation of the crystal with respect to the polarizer, the presented face of the crystal, and the size of the crystal. We show that the vibrancy of the transmitted color of the DNA-coated crystals increases with crystal thickness, noting that due to our understanding of how the crystals grow in this second step we would be able to determine a precise protocol to make large crystals of a given thickness for its desired photonic properties.This research promises to make the self-assembly of colloidal crystals much more achievable and allow for the assembly of structures of larger size than previously possible, opening a pathway towards making functional photonic devices with programmed photonic properties which is the ultimate goal of DNA-coated particle colloidal crystallization.

Photonic crystals -- a class of materials whose optical properties derive from their structure in addition to their composition -- can be created by self-assembling particles whose sizes are comparable to the wavelengths of visible light. Proof-of-principle studies have shown that DNA can be used to guide the self-assembly of micrometer-sized colloidal particles into fully programmable crystal structures with photonic properties in the visible spectrum. However, the extremely temperature-sensitive kinetics of micrometer-sized DNA-functionalized particles has frustrated attempts to grow large, monodisperse crystals that are required for photonic metamaterial applications. Here we describe a robust two-step protocol for self-assembling single-domain crystals that contain millions of optical-scale DNA-functionalized particles: Monodisperse crystals are initially assembled in monodisperse droplets made by microfluidics, after which they are grown to macroscopic dimensions via seeded diffusion-limited growth. We demonstrate the generality of our approach by assembling different macroscopic single-domain photonic crystals with metamaterial properties, like structural coloration, that depend on the underlying crystal structure. By circumventing the fundamental kinetic traps intrinsic to crystallization of optical-scale DNA-coated colloids, we eliminate a key barrier to engineering photonic devices from DNA-programmed materials.

DNA-coated colloids can self-assemble into an incredible diversity of crystal structures, but applications of this technology are limited by poor understanding and control over the dynamical crystallization pathways. To address this challenge, we use microfluidics to quantify the self-assembly dynamics of DNA-programmed colloidal crystals, from thermally-activated nucleation through reaction-limited and diffusion-limited phases of crystal growth. Our detailed measurements of the temperature and concentration dependence of the kinetics at all stages along the crystallization pathway provide a stringent test of classical theories of nucleation and growth. After accounting for the finite rolling rate of micrometer-sized DNA-coated colloids, we find that modified versions of these classical theories quantitatively predict the absolute nucleation and growth rates. We conclude by applying our model to design and demonstrate protocols for assembling large single crystals, including crystals with pronounced structural coloration, an essential step in the creation of next-generation functional materials from colloids.

We characterize two-dimensional (2D) microtubule-based active nematics driven by light-responsive kinesin motor clusters. We assess two constructs of optogenetic kinesin: opto-K401, a processive motor, and opto-K365, a non-processive motor. Measurements reveal an order of magnitude improvement in the contrast of nematic flow speeds between maximally- and minimally-illuminated states for opto-K365 motors. Focusing on opto-K365 nematics, we characterize both the steady-state flow and defect density as a function of applied light and examine the transient behavior between steady-states. The steady-state nematic flow and defect densities are set by the applied light intensity across centimeter-sized samples, independent of initial conditions. Although nematic flow reaches steady-state within tens of seconds, the defect density exhibits transient behavior for 4 to 10 minutes, showing a separation between small-scale active reorganization and system-scale structural states. This work establishes an experimental platform to test theoretical frameworks which exploit spatiotemporally-heterogeneous patterns of activity to generate targeted dynamical states.

The highly pathogenic avian influenza (HPAI) H5N1 virus clade 2.3.4.4b has caused the death of millions of domestic birds and thousands of wild birds in the USA since January 2022 (refs. 1 – 4 ). Throughout this outbreak, spillovers to mammals have been frequently documented 5 – 12 . Here we report spillover of the HPAI H5N1 virus to dairy cattle across several states in the USA. The affected cows displayed clinical signs encompassing decreased feed intake, altered faecal consistency, respiratory distress and decreased milk production with abnormal milk. Infectious virus and viral RNA were consistently detected in milk from affected cows. Viral distribution in tissues via immunohistochemistry and in situ hybridization revealed a distinct tropism of the virus for the epithelial cells lining the alveoli of the mammary gland in cows. Whole viral genome sequences recovered from dairy cows, birds, domestic cats and a raccoon from affected farms indicated multidirectional interspecies transmissions. Epidemiological and genomic data revealed efficient cow-to-cow transmission after apparently healthy cows from an affected farm were transported to a premise in a different state. These results demonstrate the transmission of the HPAI H5N1 clade 2.3.4.4b virus at a non-traditional interface, underscoring the ability of the virus to cross species barriers. Spillover of the highly pathogenic avian influenza H5N1 virus to dairy cattle and the findings of a clinical, pathological and epidemiological investigation in nine affected farms are reported.

Nicotine abuse and addiction is a major health liability. Nicotine, an active alkaloid in tobacco, is self-administered by animals and produces cellular adaptations in brain regions associated with drug reward, such as the nucleus accumbens. However, it is unknown whether, akin to illicit drugs of abuse such as cocaine or heroin, the adaptations endure and contribute to the propensity to relapse after discontinuing nicotine use. Using a rat model of cue-induced relapse, we made morphological and electrophysiological measures of synaptic plasticity, as well as quantified glutamate overflow, in the accumbens after 2 wk of withdrawal with extinction training. We found an enduring basal increase in dendritic spine head diameter and in the ratio of AMPA to NMDA currents in accumbens spiny neurons compared with yoked saline animals at 2 wk after the last nicotine self-administration session. This synaptic potentiation was associated with an increase in both AMPA (GluA1) and NMDA (GluN2A and GluN2B) receptor subunits, and a reduction in the glutamate transporter-1 (GLT-1). When nicotine seeking was reinstated by presentation of conditioned cues, there were parallel increases in behavioral responding, extracellular glutamate, and further increases in dendritic spine head diameter and ratio of AMPA to NMDA currents within 15 min. These findings suggest that targeting glutamate transmission might inhibit cue-induced nicotine seeking. In support of this hypothesis, we found that pharmacological inhibition of GluN2A with 3-Chloro-4-fluoro-N-[4-[[2-(phenylcarbonyl)hydrazino]carbonyl]benzyl]benzenesulfonamide (TCN-201) or GluN2B with ifenprodil abolished reinstated nicotine seeking. These results indicate that up-regulated GluN2A, GluN2B, and rapid synaptic potentiation in the accumbens contribute to cue-induced relapse to nicotine use.

The SARS-CoV-2 pandemic has made it clear that we have a desperate need for antivirals. We present work that the mammalian SKI complex is a broad-spectrum, host-directed, antiviral drug target. Yeast suppressor screening was utilized to find a functional genetic interaction between proteins from influenza A virus (IAV) and Middle East respiratory syndrome coronavirus (MERS-CoV) with eukaryotic proteins that may be potential host factors involved in replication. This screening identified the SKI complex as a potential host factor for both viruses. In mammalian systems siRNA-mediated knockdown of SKI genes inhibited replication of IAV and MERS-CoV. In silico modeling and database screening identified a binding pocket on the SKI complex and compounds predicted to bind. Experimental assays of those compounds identified three chemical structures that were antiviral against IAV and MERS-CoV along with the filoviruses Ebola and Marburg and two further coronaviruses, SARS-CoV and SARS-CoV-2. The mechanism of antiviral activity is through inhibition of viral RNA production. This work defines the mammalian SKI complex as a broad-spectrum antiviral drug target and identifies lead compounds for further development.

Background Multiple clades of H1N1 influenza A viruses (IAVs) circulated during the 2019–2020 season. Here, we completed serological assays to determine the specificities of serum antibodies from humans infected with viruses from different H1N1 clades during the 2019–2020 season. Methods We collected nasopharyngeal (NP) swabs and serum from influenza‐infected individuals who received care within the University of Pennsylvania Health System (UPHS). We sequenced H1N1 viruses from NP swabs and completed hemagglutination inhibition assays using serum and viruses from different H1N1 clades that we identified from NP swabs. We also collected serum samples from influenza B virus (IBV)–infected patients at UPHS, allowing us to examine antibody titers associated with H1N1 versus IBV infection. Results Sequence analyses revealed that most IAV‐infected individuals were infected with clade 6B.1A.5a.1 and 6B.1A.5a.2 H1N1 viruses that possessed substitutions at major antigenic sites of hemagglutinin. We found that antibodies from both H1N1‐ and IBV‐infected individuals recognized the 6B.1A.1 H1N1 vaccine component of the 2019–2020 vaccine more efficiently compared to the circulating 6B.1A.5a.1 and 6B.1A.5a.2 H1N1 viruses. Patients infected with 6B.1A.5a.2 clade H1N1 viruses had significantly higher titers against the vaccine strain virus, suggesting that the 6B.1A.5a.2 virus evaded antibodies elicited from previous vaccinations or infections. Conclusions These studies suggest that most individuals, irrespective of whether they were infected with H1N1 virus or IBV during the 2019–2020 season, possessed antibodies that poorly reacted to circulating H1N1 strains.