C.J. Brinker - Publications and Proceedings

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Confinement-induced quorum sensing of individual Staphylococcus aureus bacteria

Eric Carnes, DeAnna M Lopez, Niles P Donegan, Ambrose Cheung, Hattie Gresham, Graham Timmins, and C. Jeffrey Brinker

Nature Chemical Biology, November 2009 [PDF] [MEDIA COVERAGE]

It is postulated that in addition to cell density, other factors such as the dimensions and diffusional characteristics of the environment could influence quorum sensing (QS) and induction of genetic reprogramming. Modeling studies predict that QS may operate at the level of a single cell, but, owing to experimental challenges, the potential benefits of QS by individual cells remain virtually unexplored. Here we report a physical system that mimics isolation of a bacterium, such as within an endosome or phagosome during infection, and maintains cell viability under conditions of complete chemical and physical isolation. For Staphylococcus aureus, we show that quorum sensing and genetic reprogramming can occur in a single isolated organism. Quorum sensing allows S. aureus to sense confinement and to activate virulence and metabolic pathways needed for survival. To demonstrate the benefit of confinement-induced quorum sensing to individuals, we showed that quorum-sensing bacteria have significantly greater viability over non-QS bacteria.

Figure 1 | Isolation of individual S. aureus within a nanostructured droplet. (a) Schematic of physical system (not to scale) showing a cell incorporated in an endosome-like lipid vesicle within a surrounding nanostructured lipid/silica droplet deposited on glass substrate. (b) Scanning electron microscopy image of the lipid-silica hemisphere confining the cell. The nanostructure maintains cell viability under dry external conditions and allows complete chemical and physical isolation of one cell from all others. (c,d) Plan-view optical microscope images of individual cells in droplets (large outer circular areas). Magnified areas show differential interference contrast (DIC ) image and red fluorescence image of individual stained, isolated cells (both c and d) and green fluorescence image of NBD -labeled lipid localization at cell surface (c) or localized pH (d, using Oregon Green pH-sensitive dye). We find that, within the droplet, the cells become enveloped in an endosome-like lipid vesicle (c) and establish a localized pH consistent with physiological early endosomal conditions (~5.5) (d). For further information regarding aerosolassisted droplet formation and lipid localization and pH establishment, see refs. 15 and 16.

Modulus–density scaling behaviour and framework architecture of nanoporous self-assembled silicas

Hongyou Fan, Christopher Hartshorn, Thomas Buchheit, David Tallant, Roger Assink, Regina Simpson, Dave J. Kissel, Daniel J. Lacks, Salvatore Torquato, and C. Jeffrey Brinker

Nature Materials, June 2007, vol. 6, p.418-423 [PDF]

Natural porous materials such as bone, wood and pith evolved to maximize modulus for a given density1. For these threedimensional cellular solids, modulus scales quadratically with relative density2,3. But can nanostructuring improve on Nature’s designs? Here, we report modulus–density scaling relationships for cubic (C), hexagonal (H) and worm-like disordered (D) nanoporous silicas prepared by surfactantdirected self-assembly.Over the relative density range, 0.5 to 0.65, Young’s modulus scales as (density)n where n(C) <n(H) <n(D) <2, indicating that nanostructured porous silicas exhibit a structurespecific hierarchy of modulus values D < H < C. Scaling exponents less than 2 emphasize that the moduli are less sensitive to porosity than those of natural cellular solids, which possess extremal moduli based on linear elasticity theory4. Using molecular modelling and Raman and NMR spectroscopy, we show that uniform nanoscale confinement causes the silica framework of self-assembled silica to contain a higher portion of small, stiff rings than found in other forms of amorphous silica. The nanostructure-specific hierarchy and systematic increase in framework modulus we observe, when decreasing the silica framework thickness below 2 nm, provides a new ability to maximize mechanical properties at a given density needed for nanoporous materials integration5.

Logarithm of Young’s modulus versus logarithm of bulk density for self-assembled thin-film nanostructures C, H and D determined by nanoindentation. The power-law relationships of C, H and D films are E∼ ρ0.6 , E∼ ρ1.0 and E∼ ρ1.9, respectively. Modulus values were determined at a constant depth (less than 1/10 of the film thickness) where the modulus versus depth values were constant. This procedure should ensure modulus values comparable to bulk values18. Young’s modulus was calculated from the nanoindentation modulus according to Er = E(1−ν2 ), where E is Young’s modulus and ν is Poisson’s ratio. The standard deviation was determined from the mean often measurements.

Cell-Directed Assembly of Lipid-Silica Nanostructures Providing Extended Cell Viability.

Helen K. Baca, Carlee Ashley, Eric Carnes, Deanna Lopez, Jeb Flemming, Darren Dunphy, Seema Singh, Zhu Chen, Nanguo Liu, Hongyou Fan, Gabriel P. Lopez, Susan M Brozik, Magaret Werner-Washburne, C. Jeffrey Brinker

Science, Jul 21, 2006; vol. 313, p. 337-341[ PDF ] [ Supplementary Info]

Living cells combine molecular recognition, amplification, and signal transduction in an extremely small ‘package’, making them ideally suited for miniaturized, standalone, environmental or physiological sensors. However, cellular integration into devices is problematic. Cells require functional bio/inorganic interfaces, benign synthesis conditions (1-3), and external fluidic support systems or immersion in buffer to avoid dehydration. Furthermore, as recently noted by Zhang (4), it is necessary to move beyond two-dimensional (2D) adhesion in dishes to 3D architectures that better represent the extracellular matrix, enabling cells to be surrounded by other cells, maintaining fluidic accessibility, and allowing development of 3D molecular or chemical gradients.

Fig. 1. S. cerevisiae organize a lipid-rich shell that interfaces coherently with the surrounding nanostructured silica host. (A) Confocal fluorescence image of immobilized cells with 1% substitution of the fluorescently labeled lipid analog, 1-hexanoyl-2-{6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl}-snglycero-3-phosphocholine (diC6PC-NBD). Brighter areas indicate preferential concentration of lipid around cells compared to the surrounding lipid/ silica host matrix. (B and C) TEM images of cell immobilized within nanostructured lipid/silica matrix by spin-coating directly on holey carboncoatedcopper grid. (D and E) SEM of cells immobilized in silica host prepared with (D) and without (E) lipids. The dark region around the cells in (D) corresponds to an area of high carbon/phosphorus concentration consistent with the presence of lipids (fig S2). In (E), the dark region is a crevice. Cells are firmly immobilized only when the lipid interface is present. In the absence of lipid, cell washout occurs and film cracking is prevalent.