New Insight into the Chemical Nature of the Plasmonic Nanostructures Synthesized by the Reduction of Au(III) with Sulfide Species.

We have studied the products of the controversial synthesis of HAuCl4 with Na2S, which include gold nanostructures (Au NSs) that absorb in the near-infrared (NIR) region and are highly promising for photothermal therapies and other nanomedical applications. From high-resolution transmission electron microscopy, X-ray absorption spectroscopy, and small-angle X-ray scattering, we have found that only metallic Au NSs are formed as a result of this synthesis, with no detectable amount of gold sulfide or other oxidized gold species that could account for the NIR absorption. Different sulfur species are adsorbed on the Au NSs, mainly sulfides (monomeric sulfur) and polysulfides, similar to what is found on the planar gold surfaces, therefore precluding the idea that thiosulfate or other oxidized species are the actual reducing agents for Au(III) ions. The presence of strongly adsorbed S species, which are difficult to remove from the gold surface, is of great importance for their applications as regards toxicity and use of postfunctionalization strategies to anchor biomolecules and/or to increase circulation time after administration.

Spatio-temporal morphology changes in and quenching effects on the 2D spreading dynamics of cell colonies in both plain and methylcellulose-containing culture media.

To deal with complex systems, microscopic and global approaches become of particular interest. Our previous results from the dynamics of large cell colonies indicated that their 2D front roughness dynamics is compatible with the standard Kardar-Parisi-Zhang (KPZ) or the quenched KPZ equations either in plain or methylcellulose (MC)-containing gel culture media, respectively. In both cases, the influence of a non-uniform distribution of the colony constituents was significant. These results encouraged us to investigate the overall dynamics of those systems considering the morphology and size, the duplication rate, and the motility of single cells. For this purpose, colonies with different cell populations (N) exhibiting quasi-circular and quasi-linear growth fronts in plain and MC-containing culture media are investigated. For small N, the average radial front velocity and its change with time depend on MC concentration. MC in the medium interferes with cell mitosis, contributes to the local enlargement of cells, and increases the distribution of spatio-temporal cell density heterogeneities. Colony spreading in MC-containing media proceeds under two main quenching effects, I and II; the former mainly depending on the culture medium composition and structure and the latter caused by the distribution of enlarged local cell domains. For large N, colony spreading occurs at constant velocity. The characteristics of cell motility, assessed by measuring their trajectories and the corresponding velocity field, reflect the effect of enlarged, slow-moving cells and the structure of the medium. Local average cell size distribution and individual cell motility data from plain and MC-containing media are qualitatively consistent with the predictions of both the extended cellular Potts models and the observed transition of the front roughness dynamics from a standard KPZ to a quenched KPZ. In this case, quenching effects I and II cooperate and give rise to the quenched-KPZ equation. Seemingly, these results show a possible way of linking the cellular Potts models and the 2D colony front roughness dynamics.

Dynamic scaling analysis of two-dimensional cell colony fronts in a gel medium: a biological system approaching a quenched Kardar-Parisi-Zhang universality.

The interfacial two-dimensional spreading dynamics of quasilinear Vero cell colony fronts in methylcellulose (MC)-containing culture medium, under a constant average front displacement velocity regime, was investigated. Under comparable experimental conditions, the average colony front displacement velocity becomes lower than that reported for a standard culture medium. Initially, the presence of MC in the medium hinders both the colony spreading, due to a gradual change in the average size and shape of cells and their distribution in the colony, and the cell motility in the gelled medium. Furthermore, at longer culture times enlarged cells appear at random in the border region of the colony. These cells behave as obstacles (pinning sites) for the displacement of smaller cells towards the colony front. The dynamic scaling analysis of rough fronts yields the set of exponents α=0.63±0.04,ß=0.75±0.05, and z=0.84±0.05, which is close to that expected for a quenched Kardar-Parisi-Zhang model.

Growth dynamics of cancer cell colonies and their comparison with noncancerous cells.

The two-dimensional (2D) growth dynamics of HeLa (cervix cancer) cell colonies was studied following both their growth front and the pattern morphology evolutions utilizing large population colonies exhibiting linearly and radially spreading fronts. In both cases, the colony profile fractal dimension was d(f)=1.20±0.05 and the growth fronts displaced at the constant velocity 0.90±0.05 µm min(-1). Colonies showed changes in both cell morphology and average size. As time increased, the formation of large cells at the colony front was observed. Accordingly, the heterogeneity of the colony increased and local driving forces that set in began to influence the dynamics of the colony front. The dynamic scaling analysis of rough colony fronts resulted in a roughness exponent α = 0.50±0.05, a growth exponent ß = 0.32±0.04, and a dynamic exponent z=1.5±0.2. The validity of this set of scaling exponents extended from a lower cutoff l(c)≈60 µm upward, and the exponents agreed with those predicted by the standard Kardar-Parisi-Zhang continuous equation. HeLa data were compared with those previously reported for Vero cell colonies. The value of d(f) and the Kardar-Parisi-Zhang-type 2D front growth dynamics were similar for colonies of both cell lines. This indicates that the cell colony growth dynamics is independent of the genetic background and the tumorigenic nature of the cells. However, one can distinguish some differences between both cell lines during the growth of colonies that may result from specific cooperative effects and the nature of each biosystem.

Dynamics and morphology characteristics of cell colonies with radially spreading growth fronts.

The dynamics of two-dimensional (2D) radially spreading growth fronts of Vero cell colonies was investigated utilizing two types of colonies, namely type I starting from clusters with a small number of cells, which initially exhibited arbitrary-shaped rough growth fronts and progressively approached quasicircular ones as the cell population increased; and type II colonies, starting from a relatively large circular three-dimensional (3D) cell cluster. For large cell population colonies, the fractal dimension of the fronts was D(F) = 1.20±0.05. For low cell populations, the mean colony radius increased exponentially with time, but for large ones the constant radial front velocity 0.20±0.02 µm min(-1) was reached. Colony spreading was accompanied by changes in both cell morphology and average size, and by the formation of very large cells, some of them multinuclear. Therefore the heterogeneity of colonies increased and local driving forces that set in began to influence the 2D growth front kinetics. The retardation effect related to the exponential to constant radial front velocity transition was assigned to a number of possible interferences including the cell duplication and 3D growth in the bulk of the colony. The dynamic scaling analysis of overhang-corrected rough colony fronts, after arc-radius coordinate system transformation, resulted in roughness exponent α = 0.50±0.05 and growth exponent ß = 0.32±0.04, for arc lengths greater than 100 µm. This set of scaling exponents agreed with that predicted by the Kardar, Parisi, and Zhang continuous equation. For arc lengths shorter than 2-3 cell diameters, the value α = 0.85±0.05 would be related to a cell front roughening caused by temporarily membrane deformations occasionally interfered by cell proliferation.

Morphology and dynamic scaling analysis of cell colonies with linear growth fronts.

The growth of linear cell colony fronts is investigated from the morphology of cell monolayer colonies, the cell size and shape distribution, the front displacement velocity, and the dynamic scaling analysis of front roughness fluctuations. At the early growth stages, colony patterns consist of rather ordered compact domains of small cells, whereas at advanced stages, an uneven distribution of cells sets in, and some large cells and cells exhibiting large filopodia are produced. Colony front profiles exhibit overhangs and behave as fractals with the dimension D(F)=1.25±0.05. The colony fronts shift at 0.22±0.02 µm min(-1) average constant linear velocity and their roughness (w) increases with time (t). Dynamic scaling analysis of experimental and overhang-corrected growth profile data shows that w versus system width l log-log plots collapse to a single curve when l exceeds a certain threshold value l(o), a width corresponding to the average diameter of few cells. Then, the influence of overhangs on the roughness dynamics becomes negligible, and a growth exponent ß=0.33±0.02 is derived. From the structure factor analysis of overhang-corrected profiles, a global roughness exponent α(s)=0.50±0.05 is obtained. For l>200 µm, this set of exponents fulfills the Family-Vicsek relationship. It is consistent with the predictions of the continuous Kardar-Parisi-Zhang model.