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Malaria pathogenesis and parasite multiplication depend on the ability of Plasmodium merozoites to invade human erythrocytes. Invasion is a complex multi-step process involving multiple parasite proteins which can differ between species and has been most extensively studied in P. falciparum. However, dissecting the precise role of individual proteins has to date been limited by the availability of quantifiable phenotypic assays. In this study, we apply a new approach to assigning function to invasion proteins by using optical tweezers to directly manipulate recently egressed P. falciparum merozoites and erythrocytes and quantify the strength of attachment between them, as well as the frequency with which such attachments occur. Using a range of inhibitors, antibodies, and genetically modified strains including some generated specifically for this work, we quantitated the contribution of individual P. falciparum proteins to these merozoite-erythrocyte attachment interactions. Conditional deletion of the major P. falciparum merozoite surface protein PfMSP1, long thought to play a central role in initial attachment, had no impact on the force needed to pull merozoites and erythrocytes apart, whereas interventions that disrupted the function of several members of the EBA-175 like Antigen (PfEBA) family and Reticulocyte Binding Protein Homologue (PfRH) invasion ligand families did have a significant negative impact on attachment. Deletion of individual PfEBA and PfRH ligands reinforced the known redundancy within these families, with the deletion of some ligands impacting detachment force while others did not. By comparing over 4000 individual merozoite-erythrocyte interactions in a range of conditions and strains, we establish that the PfEBA/PfRH families play a central role in P. falciparum merozoite attachment, not the major merozoite surface protein PfMSP1. Author summary: Malaria is a devastating disease caused by a parasitic infection. The deadliest species is Plasmodium falciparum, which causes more than 600,000 deaths annually. The Plasmodium life cycle is complex, but all the symptoms of malaria are caused when the parasites replicate in human red blood cells. Replication depends on the invasion of the red blood cells by the parasites, a process involving multiple molecular interactions and multiple steps. Invasion begins with the attachment of the parasite to the red blood cell, making this step of particular interest in the development of new therapeutics. We used an optical tweezer assay to directly measure the binding force between individual parasites and red blood cells, and combined this assay with a range of molecular and genetic tools that target specific interactions known to have a role in invasion. This approach showed that loss of a protein commonly thought to be critical to the early stages of invasion, PfMSP1, had no effect on attachment strength, whereas disruptions of several members from two families of proteins (the Erythrocyte Binding Like protein family and the Reticulocyte Binding-like protein family) did affect attachment strength. [ABSTRACT FROM AUTHOR]

Three-dimensional crystalline frameworks with nanoscale periodicity are valuable for many emerging technologies, from nanophotonics to nanomedicine. DNA nanotechnology has emerged as a prime route for constructing these materials, with most approaches taking advantage of the structural rigidity and bond directionality programmable for DNA building blocks. Recently, we have introduced an alternative strategy reliant on flexible, amphiphilic DNA junctions dubbed C-stars, whose ability to crystallize is modulated by design parameters, such as nanostructure topology, conformation, rigidity, and size. While C-stars have been shown to form ordered phases with controllable lattice parameter, response to stimuli, and embedded functionalities, much of their vast design space remains unexplored. Here, we investigate the effect of changing the chemical nature of the hydrophobic modifications and the structure of the DNA motifs in the vicinity of these moieties. While similar design variations should strongly alter key properties of the hydrophobic interactions between C-stars, such as strength and valency, only limited differences in self-assembly behavior are observed. This finding suggests that long-range order in C-star crystals is likely imposed by structural features of the building block itself rather than the specific characteristics of the hydrophobic tags. Nonetheless, we find that altering the hydrophobic regions influences the ability of C-star crystals to uptake hydrophobic molecular cargoes, which we exemplify by studying the encapsulation of antibiotic penicillin V. Besides advancing our understanding of the principles governing the self-assembly of amphiphilic DNA building blocks, our observations thus open up new routes to chemically program the materials without affecting their structure. [ABSTRACT FROM AUTHOR]

Synchronization of driven oscillators is a key aspect of flow generation in artificial and biological filaments such as cilia. Previous theoretical and numerical studies have considered the "rotor" model of a cilium in which the filament is coarse grained into a colloidal sphere driven with a given force law along a predefined trajectory to represent the oscillating motion of the cilium. These studies pointed to the importance of two factors in the emergence of synchronization: the modulation of the driving force around the orbit and the deformability of the trajectory. In this work it is shown via experiments, supported by numerical simulations and theory, that both of these factors are important and can be combined to produce strong synchronization (within a few cycles) even in the presence of thermal noise. [ABSTRACT FROM AUTHOR]

Motile cilia are highly conserved structures in the evolution of organisms, generating the transport of fluid by periodic beating, through remarkably organized behavior in space and time. It is not known how these spatiotemporal patterns emerge and what sets their properties. Individual cilia are nonequilibrium systems with many degrees of freedom. However, their description can be represented by simpler effective force laws that drive oscillations, and paralleled with nonlinear phase oscillators studied in physics. Here a synthetic model of two phase oscillators, where colloidal particles are driven by optical traps, proves the role of the average force profile in establishing the type and strength of synchronization. We find that highly curved potentials are required for synchronization in the presence of noise. The applicability of this approach to biological data is also illustrated by successfully mapping the behavior of cilia in the alga Chlamydomonas onto the coarse-grained model. [ABSTRACT FROM AUTHOR]

Optical tweezers are used to manipulate the shape of artificial dioleoyl-phosphatidylcholine (DOPC) phospholipid vesicles of around 30µm diameter. Using a time-shared trapping system, a complex of traps drives oscillations of the vesicle equator, with a sinusoidal time dependence and over a range of spatial and temporal frequencies. The mechanical response of the vesicle membrane as a function of the frequency and wavelength of the driving oscillation is monitored. A simple model of the vesicles as spherical elastic membranes immersed in a Newtonian fluid, driven by a harmonic trapping potential, describes the experimental data. The bending modulus of the membrane is recovered. The method has potential for future investigation of nonthermally driven systems, where comparison of active and passive rheology can help to distinguish nonthermal forces from equilibrium fluctuations. [ABSTRACT FROM AUTHOR]

Magneto-optical tweezers have been constructed and used for studying interactions between colloids in nematic liquid crystals. We used super-paramagnetic beads which induced planar anchoring at the surface and were suitable for optical trapping as well as manipulation by external magnetic field. Depending on the thickness of the sample, attractive or repulsive forces between two immersed spheres were observed: repulsive for sample thickness comparable to the bead size, and attractive in thick samples. This behaviour corresponds to quadrupolar interaction between two beads. [ABSTRACT FROM AUTHOR]

A stroboscope designed to observe pulsars in the optical spectrum is presented. The absolute phase of the stroboscope is synchronized to better than 2.5 μs with the known radio ephemerides for a given pulsar. The absolute timing is provided by the Global Positioning System clock. With such a device resolved photometry of pulsars can be performed. We demonstrated the instrument’s capabilities with the results of a set of observations of the Crab pulsar, the brightest of the known optical pulsars, with a visual magnitude of 16.5, and a rotational frequency of ∼29 Hz. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

A number of colloidal systems, including polymers, proteins, micelles and hard spheres, have been studied in thermal gradients to observe and characterize their driven motion. Here we show experimentally the thermophoretic behaviour of unilamellar lipid vesicles, finding that mobility depends on the mean local temperature of the suspension and on the structure of the exposed polar lipid head groups. By tuning the temperature, vesicles can be directed towards hot or cold, forming a highly concentrated region. Binary mixtures of vesicles composed of different lipids can be segregated using thermophoresis, according to their head group. Our results demonstrate that thermophoresis enables robust and chemically specific directed motion of liposomes, which can be exploited in driven processes. [ABSTRACT FROM AUTHOR]

Using videomicroscopy imaging, we demonstrate the existence of a short-ranged equilibrium attraction between heavy silica colloids diffusing on soft surfaces of cross-linked polymer gels. The intercolloid potential can be tuned by changing the gel stiffness or by coating the colloids with a polymer layer. On sufficiently soft substrates, the interaction induced by the polymer matrix leads to large-scale colloidal aggregation. We correlate the in-plane interaction with a colloid-surface attraction. [ABSTRACT FROM AUTHOR]