In this feature article, gold nanoparticle conjugates loaded with phthalocyanine-based PDT drugs are prepared and tested for delivery efficiency and PDT efficacy on HeLa cancer cells. It could be shown that the delivery and PDT outcome are strongly affected by the bond that links the drug load to the nanoparticle surface. Whereas labile amino adsorption to the Au nanoparticle surface allows for efficient drug release into the cancer cells and for efficient PDT, a covalent thiol bond to the Au nanoparticle leads to the delivery of the drug into cell vesicles, and no PDT effect is observed. This work highlights the importance of carefully choosing the interaction between drug molecules and the nanoparticle surface.

Considerable experimental evidence indicates that the primary, nonmotile cilium is a mechanosensory organelle in several epithelial cell types. As the relationship between cellular responses and nature and magnitude of applied forces is not well understood, we have investigated the effects of exposure of monolayers of renal collecting duct chief cells to orbital shaking and quantified the forces incident on cilia. An exposure of 24 h of these cells to orbital shaking resulted in a decrease of amiloride-sensitive sodium current by approximately 60% and ciliary length by approximately 30%. The sensitivity of the sodium current to shaking was dependent on intact cilia. The drag force on cilia due to induced fluid flow during orbital shaking was estimated at maximally 5.2x10(-3) pN at 2 Hz, approximately 4 times that of thermal noise. The major structural feature of cilia contributing to their sensitivity appears to be ciliary length. As more than half of the total drag force is exerted on the ciliary cap, one function of the slender stalk may be to expose the cap to greater drag force. Regardless, the findings indicate that the cilium is a mechanosensory organelle with a sensitivity much lower than previously recognized.

Hydrothermal waves in a liquid bridge with aspect ratio near the Rayleigh limit under microgravityThe bifurcation of the solutions of the nonlinear equilibrium problem of a weightless liquid bridge with a free surface pinned to the edges of two coaxial equidimensional circular disks is examined. The bifurcation is studied in the neighborhood of the stability boundary for axisymmetric equilibrium states with emphasis on the boundary segment corresponding to nonaxisymmetric critical perturbations. The first approximations for the shapes of the bifurcated equilibrium surfaces are obtained. The stability of the bifurcated states is then determined from the bifurcation structure. Along the maximum volume stability limit, depending on values of the system parameters, loss of stability with respect to nonaxisymmetric perturbations results in either a jump or a continuous transition to stable nonaxisymmetric shapes. The value of the slenderness at which a change in the type of transition occurs is found to be ⌳ s ϭ0.4946. Experimental investigation based on a neutral buoyancy technique agrees with this prediction. It shows that, for ⌳Ͻ⌳ s , the jump is finite and that a critical bridge undergoes a finite deformation to a stable nonaxisymmetric state.

Primary cilia are ubiquitous mammalian cellular substructures implicated in an ever-increasing number of regulatory pathways. The well-established ciliary hypothesis states that physical bending of the cilium (for example, due to fluid flow) initiates signaling cascades, yet the mechanical properties of the cilium remain incompletely measured, resulting in confusion regarding the biological significance of flow-induced ciliary mechanotransduction. In this work we measure the mechanical properties of a primary cilium by using an optical trap to induce resonant oscillation of the structure. Our data indicate 1) the primary cilium is not a simple cantilevered beam; 2) the base of the cilium may be modeled as a nonlinear rotatory spring, with the linear spring constant k of the cilium base calculated to be (4.6 ± 0.62) × 10(-12) N/rad and nonlinear spring constant α to be (-1 ± 0.34) × 10(-10) N/rad(2); and 3) the ciliary base may be an essential regulator of mechanotransduction signaling. Our method is also particularly suited to measure mechanical properties of nodal cilia, stereocilia, and motile cilia-anatomically similar structures with very different physiological functions.

The ciliary/flagellar system is perhaps unique in biology in that not only are biochemical manipulations used to elucidate the function, but physical manipulations as well. Thus, there is a considerable need to have an integrated physical-biochemical model of a cilium and its function. The emphasis of this paper will be to firstly, provide a mechanistic picture of the cilium and its environment because the biological community is perhaps less aware of this type of model development, and second, to point the way towards future experiments that will elucidate the role of the cilium in organ and organism level signaling and regulation.

Although solitary or sensory cilia are present in most cells of the body and their existence has been known since the sixties, very little is known about their functions. One suspected function is fluid flow sensing- physical bending of cilia produces an influx of Ca++, which can then result in a variety of activated signaling pathways. Defective cilia and ciliary-associated proteins have been shown to result in cystic diseases. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive disease, typically appearing in the 5th decade of life and is one of the most common monogenetic inherited human diseases, affecting approximately 600,000 people in the United States. Because the mechanical properties of cilia impact their response to applied flow, we asked how the stiffness of cilia can be controlled pharmacologically. We performed an experiment subjecting cilia to Taxol (a microtubule stabilizer) and CoCl2 (a HIF stabilizer to model hypoxia). Madin-Darby Canine Kidney (MDCK) cells were selected as our model system. After incubation with a selected pharmacological agent, cilia were optically trapped and the bending modulus measured. We found that HIF stabilization significantly weakens cilia. These results illustrate a method to alter the mechanical properties of primary cilia and potentially alter the flow sensing properties of cilia.

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A space-borne optical tweezer apparatus for use with colloidal crystallization experiments has been characterized. The trapping force has been measured as a function of index mismatch between colloidal microspheres and the surrounding fluid and as a function of particle size. This work also presents a method to determine the refractive index of a colloidal microsphere, which is then used to calculate the applied trapping force for the case of an arbitrary background fluid. This is useful for work with dense colloidal suspensions when the usual (e.g., Stokes flow) trap force measurement methods do not apply, as well as microrheological studies of complex soft matter.