Marta Tello

Biomechanical Remodeling of the Microenvironment by Stromal Caveolin-1 Favors Tumor Invasion and Metastasis

Mechanotransduction is a key determinant of tissue homeostasis and tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1 fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intratumoral microenvironments to facilitate tumor invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment.

Nano-oxidation of silicon surfaces: Comparison of noncontact and contact atomic-force microscopy methods

Local oxidation lithography by atomic-force microscopy is emerging as a powerful method for nanometer-scale patterning of surfaces. Here, we perform a comparative study of contact and noncontact atomic-force microscopy (AFM) oxidation experiments. The comparison of height and width dependencies on voltage and pulse duration allows establishing noncontact AFM as the optimum local oxidation method. For the same electrical conditions, noncontact AFM oxides exhibit higher aspect ratios (0.04 vs 0.02). The smallness of the liquid meniscus in noncontact AFM oxidation produces smaller oxide widths. We also report a slower oxidation rate in contact AFM oxidation. We explain this result by introducing an effective energy barrier (∼0.14 eV) that includes the mechanical work done by the growing oxide against the cantilever (∼0.01 eV).

Size determination of field-induced water menisci in noncontact atomic force microscopy

We have studied the dimensions of water capillaries formed by an applied electrical field between an atomic force microscope tip and a flat silicon surface. The lateral and vertical dimensions of the liquid meniscus are in the 5–30 nm range. The size depends on the duration and strength of the voltage pulse. It increases by increasing the voltage strength or the pulse duration. The meniscus size is deduced from the experimental measurement of the snap-off separation. These results are of special relevance to optimize local oxidation nanolithography.

Fabrication of gold nanowires on insulating substrates by field-induced mass transport

A method for the fabrication of nanometer size gold wires on insulating surfaces is presented. An oscillating gold-coated atomic force microscope tip is brought into close proximity of a silicon dioxide surface. The application of a negative sample voltage produces the transport of gold atoms from the tip to the surface. The voltage is applied when there is a tip–surface separation of ∼3 nm. The finite tip–surface separation enhances the tip lifetime. It also allows the application of sequences of multiple voltage pulses. Those sequences allow the fabrication of continuous nanowires. The atomic force microscope gold deposition is performed at room temperature and in ambient conditions which makes the method fully compatible with standard lithographic techniques. Electron transport measurements of the wires show a clear metallic behavior. Electrical resistivities of ∼3×10−7 Ω m and current densities of up to 5×1011 A m−2 are reported.

Giant growth rate in nano-oxidation of p-silicon surfaces by using ethyl alcohol liquid bridges

We demonstrate that local oxidation nanolithography can be performed in liquid environments different from aqueous solutions with a significant improvement in the aspect ratio of the fabricated motives. Here, we perform a comparative study of noncontact atomic force microscopy oxidation experiments in water and ethyl alcohol. The growth rate of local oxides can be increased by almost an order of magnitude by using oxyanions from ethyl alcohol molecules. We propose that the enhanced growth rate is a consequence of the reduction of the trapped charges within the growing oxide. The present results open the possibility of using local oxidation nanolithography to directly fabricate vertical oxide structures while keeping lateral sizes in the nanometer range.

Linewidth determination in local oxidation nanolithography of silicon surfaces

We measure the linewidth of structures fabricated by local oxidation lithography on silicon surfaces. Two different structures, isolated and arrays of parallel lines have been generated. The oxide structures have been fabricated in the proximity of sexithiophene islands whose size is comparable to the oxide motives. The comparison between local oxides and sexithiophene islands reveals that atomic force microscopy (AFM) images faithfully reproduce the size and shape of local silicon oxides. The oxide lines have a trapezoidal shape with a flat section at the top. AFM images of the oxide structures show rather small slopes ∼0.05–0.15 which imply angles with the horizontal between 3° and 8°. The shallow angles imply a minimum feature size of 14 nm at the base for an oxide thickness of 1 nm. Linewidths of 7 nm and 20 nm at the top and base, respectively, have been fabricated. We have also demonstrated the ability to pack structures with a periodicity of 13 nm.

Dynamical approach to molecular movements in (C14H29NH3)2ZnCl4 above room temperature

Calorimetric, thermal expansion, dielectric and optical measurements reveal an interesting sequence of phase transitions from a quasi-ordered phase at room temperature up to an isotropic liquid phase above 438K. In the first phase transition there is an interchange between high and low refraction indexes. The second is an order-disorder phase transition. In the third, an important configurational change occurs which finally leads the crystal to an isotropic liquid phase. This sequence is interpreted within the scope of a phenomenological approach.

A wide temperature range photoacoustic cell for the study of phase transitions in solids: an application to the ferroelectric-incommensurate (N(CH3)4)2CoCl4

A resonant photoacoustic cell which allows for amplitude and phase measurements over a wide temperature range is described. Photoacoustic measurements prove to be highly sensitive for the study of phase transitions in solids as well as the behaviour of the thermal conductivity. An application to the ferroelectric-incommensurate (N(CH3)4)2CoCl4 is carried out.

Generating and characterizing the mechanical properties of cell-derived matrices using atomic force microscopy

Mechanical interaction between cells and their surrounding extracellular matrix (ECM) controls key processes such as proliferation, differentiation and motility. For many years, two-dimensional (2D) models were used to better understand the interactions between cells and their surrounding ECM. More recently, variation of the mechanical properties of tissues has been reported to play a major role in physiological and pathological scenarios such as cancer progression. The 3D architecture of the ECM finely tunes cellular behavior to perform physiologically relevant tasks. Technical limitations prevented scientists from obtaining accurate assessment of the mechanical properties of physiologically realistic matrices. There is therefore a need for combining the production of high-quality cell-derived 3D matrices (CDMs) and the characterization of their topographical and mechanical properties. Here, we describe methods that allow to accurately measure the young modulus of matrices produced by various cellular types. In the first part, we will describe and review several protocols for generating CDMs matrices from endothelial, epithelial, fibroblastic, muscle and mesenchymal stem cells. We will discuss tools allowing the characterization of the topographical details as well as of the protein content of such CDMs. In a second part, we will report the methodologies that can be used, based on atomic force microscopy, to accurately evaluate the stiffness properties of the CDMs through the quantification of their young modulus. Altogether, such methodologies allow characterizing the stiffness and topography of matrices deposited by the cells, which is key for the understanding of cellular behavior in physiological conditions.

Influence of the thermal expansion on the piezoelectric photoacoustic detection of ferro-paraelastic phase transition in (CH3CH2NH3)2 CuCl4

The ferro-paraelastic phase transition of (CH3CH2NH3)2 CuCl4 is studied by means of the photoacoustic (PA) technique using a piezoelectric detection system. Both the PA amplitude and phase exhibit a particularly unusual behaviour at the transition temperature, which is explained in terms of the dependence of the PA signal on the thermal expansion coefficient when the piezoelectric method is applied. Previously reported specific heat values together with additional measurements of the expansion coefficient allow the authors to obtain a quantitative adjustment of the PA amplitude curve in reasonable agreement with the experimental results.