The phase behavior of confined water is a topic of intense and current interest due to its relevance in biology, geology, and materials science. Nevertheless, little is known about the phases that water forms even when confined in the simplest geometries, such as water confined between parallel surfaces. Here we use molecular dynamics simulations to compute the phase diagram of two layers of water confined between parallel non hydrogen bonding walls. This study shows that the water bilayer forms a dodecagonal quasicrystal, as well as two previously unreported bilayer crystals, one tiled exclusively by pentagonal rings. Quasicrystals, structures with long-range order but without periodicity, have never before been reported for water. The dodecagonal quasicrystal is obtained from the bilayer liquid through a reversible first-order phase transition and has diffusivity intermediate between that of the bilayer liquid and ice phases. The water quasicrystal and the ice polymorphs based on pentagons are stabilized by compression of the bilayer and are not templated by the confining surfaces, which are smooth. This demonstrates that these novel phases are intrinsically favored in bilayer water and suggests that these structures could be relevant not only for confined water but also for the wetting and properties of water at interfaces.

Confinement of water usually depresses its melting temperature. Here we use molecular dynamics simulations to determine the liquid-crystal equilibrium temperature for water confined between parallel hydrophobic or mildly hydrophilic plates as a function of the distance between the surfaces. We find that bilayer ice, an ice polymorph in which the local environment of each water molecule strongly departs from the most stable tetrahedral structure, has the highest melting temperature (T(m)) of the series of l-layer ices. The melting temperature of bilayer ice is not only unusually high compared to the other confined ices, but also above the melting point of bulk hexagonal ice. Recent force microscopy experiments of water confined between graphite and a tungsten tip reveal the formation of ice at room temperature [K. B. Jinesh and J. W. M. Frenken, Phys. Rev. Lett. 101, 036101 (2008)]. Our results suggest that bilayer ice, for which we compute a T(m) as high as 310 K in hydrophobic confinement, is the crystal formed in those experiments.

Exosomes and microvesicles are two classes of submicroscopic vesicle released by cells into the extracellular space. Collectively referred to as extracellular vesicles, these membrane containers facilitate important cell-cell communication by carrying a diverse array of signaling molecules, including nucleic acids, proteins, and lipids. Recently, the role of extracellular vesicle signaling in cancer progression has become a topic of significant interest. Methods to detect and target exosomes and microvesicles are needed to realize applications of extracellular vesicles as biomarkers and, perhaps, therapeutic targets. Detection of exosomes and microvesicles is a complex problem as they are both submicroscopic and of heterogeneous cellular origins. In this Minireview, we highlight the basic biology of extracellular vesicles, and address available biochemical and biophysical detection methods. Detectible characteristics described here include lipid and protein composition, and physical properties such as the vesicle membrane shape and diffusion coefficient. In particular, we propose that detection of exosome and microvesicle membrane curvature with lipid chemical probes that sense membrane shape is a distinctly promising method for identifying and targeting these vesicles.

Toll-like receptor (TLR) agonists activate both the innate and the adaptive immune systems. These TLR agonists have been exploited as potent vaccine adjuvants and antitumor agents. We describe the identification and characterization of a small molecule, N-methyl-4-nitro-2-(4-(4-(trifluoromethyl)phenyl)-1 H-imidazol-1-yl)aniline (CU-T12-9), that directly targets TLR1/2 to initiate downstream signaling. CU-T12-9 specifically induces TLR1/2 activation, which can be blocked by either the anti-hTLR1 or the anti-hTLR2 antibody, but not the anti-hTLR6 antibody. Using a variety of different biophysical assays, we have demonstrated the binding mode of CU-T12-9. By binding to both TLR1 and TLR2, CU-T12-9 facilitates the TLR1/2 heterodimeric complex formation, which in turn activates the downstream signaling. Fluorescence anisotropy assays revealed competitive binding to the TLR1/2 complex between CU-T12-9 and Pam3CSK4 with a half-maximal inhibitory concentration (IC50) of 54.4 nM. Finally, we showed that CU-T12-9 signals through nuclear factor κB (NF-κB) and invokes an elevation of the downstream effectors tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and inducible nitric oxide synthase (iNOS). Thus, our studies not only provide compelling new insights into the regulation of TLR1/2 signaling transduction but also may facilitate future therapeutic developments.

Carbonaceous surfaces are a major source of atmospheric particles and could play an important role in the formation of ice. Here we investigate through molecular simulations the stability, metastability, and molecular pathways of deposition of amorphous ice, bilayer ice, and ice I from water vapor on graphitic and atomless Lennard-Jones surfaces as a function of temperature. We find that bilayer ice is the most stable ice polymorph for small cluster sizes, nevertheless it can grow metastable well above its region of thermodynamic stability. In agreement with experiments, the simulations predict that on increasing temperature the outcome of water deposition is amorphous ice, bilayer ice, ice I, and liquid water. The deposition nucleation of bilayer ice and ice I is preceded by the formation of small liquid clusters, which have two wetting states: bilayer pancake-like (wetting) at small cluster size and droplet-like (non-wetting) at larger cluster size. The wetting state of liquid clusters determines which ice polymorph is nucleated: bilayer ice nucleates from wetting bilayer liquid clusters and ice I from non-wetting liquid clusters. The maximum temperature for nucleation of bilayer ice on flat surfaces, T(B)(max) is given by the maximum temperature for which liquid water clusters reach the equilibrium melting line of bilayer ice as wetting bilayer clusters. Increasing water-surface attraction stabilizes the pancake-like wetting state of liquid clusters leading to larger T(B)(max) for the flat non-hydrogen bonding surfaces of this study. The findings of this study should be of relevance for the understanding of ice formation by deposition mode on carbonaceous atmospheric particles, including soot.