How Do Cells Make Decisions: Engineering Micro- and Nanoenvironments for Cell Migration

Cell migration contributes to cancer metastasis and involves cell adhesion to the extracellular matrix (ECM), force generation through the cell's cytoskeletal, and finally cell detachment. Both adhesive cues from the ECM and soluble cues from neighbouring cells and tissue trigger intracellular signalling pathways that are essential for cell migration. While the machinery of many signalling pathways is relatively well understood, how hierarchies of different and conflicting signals are established is a new area of cellular cancer research. We examine the recent advances in microfabrication, microfluidics, and nanotechnology that can be utilized to engineer micro- and nanoscaled cellular environments. Controlling both adhesive and soluble cues for migration may allow us to decipher how cells become motile, choose the direction for migration, and how oncogenic transformations influences these decision-making processes

A global database for metacommunity ecology, integrating species, traits, environment and space

The use of functional information in the form of species traits plays an important role in explaining biodiversity patterns and responses to environmental changes. Although relationships between species composition, their traits, and the environment have been extensively studied on a case-by-case basis, results are variable, and it remains unclear how generalizable these relationships are across ecosystems, taxa and spatial scales. To address this gap, we collated 80 datasets from trait-based studies into a global database for metaCommunity Ecology: Species, Traits, Environment and Space; “CESTES”. Each dataset includes four matrices: species community abundances or presences/absences across multiple sites, species trait information, environmental variables and spatial coordinates of the sampling sites. The CESTES database is a live database: it will be maintained and expanded in the future as new datasets become available. By its harmonized structure, and the diversity of ecosystem types, taxonomic groups, and spatial scales it covers, the CESTES database provides an important opportunity for synthetic trait-based research in community ecology

The Relative Importance of Topography and RGD Ligand Density for Endothelial Cell Adhesion

The morphology and function of endothelial cells depends on the physical and chemical characteristics of the extracellular environment. Here, we designed silicon surfaces on which topographical features and surface densities of the integrin binding peptide arginine-glycine-aspartic acid (RGD) could be independently controlled. We used these surfaces to investigate the relative importance of the surface chemistry of ligand presentation versus surface topography in endothelial cell adhesion. We compared cell adhesion, spreading and migration on surfaces with nano- to micro-scaled pyramids and average densities of 6×102–6×1011 RGD/mm2. We found that fewer cells adhered onto rough than flat surfaces and that the optimal average RGD density for cell adhesion was 6×105 RGD/mm2 on flat surfaces and substrata with nano-scaled roughness. Only on surfaces with micro-scaled pyramids did the topography hinder cell migration and a lower average RGD density was optimal for adhesion. In contrast, cell spreading was greatest on surfaces with 6×108 RGD/mm2 irrespectively of presence of feature and their size. In summary, our data suggest that the size of pyramids predominately control the number of endothelial cells that adhere to the substratum but the average RGD density governs the degree of cell spreading and length of focal adhesion within adherent cells. The data points towards a two-step model of cell adhesion: the initial contact of cells with a substratum may be guided by the topography while the engagement of cell surface receptors is predominately controlled by the surface chemistry

Advanced Materials and Devices for the Regulation and Study of NK Cells

Natural Killer (NK) cells are innate lymphocytes that contribute to immune protection by cytosis, cytokine secretion, and regulation of adaptive responses of T cells. NK cells distinguish between healthy and ill cells, and generate a cytotoxic response, being cumulatively regulated by environmental signals delivered through their diverse receptors. Recent advances in biomaterials and device engineering paved the way to numerous artificial microenvironments for cells, which produce synthetic signals identical or similar to those provided by the physiological environment. In this paper, we review recent advances in materials and devices for artificial signaling, which have been applied to regulate NK cells, and systematically study the role of these signals in NK cell function

Modified silicon surfaces for controlled cell interactions

Vital cellular processes such as adhesion, migration, differentiation and apoptosis are closely dependent on the interaction of the integrin receptors present on the outer membrane of cells with proteins that compose the extracellular matrix (ECM). The peptide sequence Arg–Gly–Asp (RGD), present in many of the extracellular proteins, has been found to play a dominating role in cell adhesion, where the integrin–RGD ligand system acts as an anchoring point to the substratum. Importantly, clusters of RGD–engaged integrin, called focal adhesions, act as plugs that induce multiple intracellular signaling pathways which regulate cell behavior. The ECM displays diverse chemical and topographical environments. Understanding how RGD ligand density, topography and ligand clustering modulate cell behavior is therefore crucial for research in cancer as well as for biomaterials or biosensors. The present work describes how modified silicon surfaces can be used to mimic the chemical and topographical aspects of the ECM. Investigating specific cell–surface interactions requires 1) RGD ligands with adjustable surface densities presented atop a bio–inert background, 2) control over substrate topography while ensuring the integrity of surface chemistry, 3) explicit distribution of RGD ligands in spots of tuneable sizes and numbers. Based on the hydrosilylation of 1-alkene moieties on silicon, biocompatible multilayer systems that meet these criteria are constructed and characterized. The spacing of RGD ligands of 50–100 nm is shown to influence the phenotype of endothelial cells and thus demonstrates the vital role of the spatial arrangement of ECM motifs in angiogenesis. Furthermore, even though cells display the expected behavior towards surface roughness, these remain sensitive to variations in RGD ligand spacing, suggesting that the spatial arrangement of the ECM motifs and substrate topography are not codependent. Finally, it is revealed that cells are less sensitive to RGD ligand spacing when integrins have the possibility to form localized clusters and hence, that integrin clustering balances the effects of ligand spacing on cell response

A Comparative study of modifying gold and carbon electrode with 4-sulfophenyl diazonium salt

A comparison of the reductive adsorption behavior of 4-sulfophenyl diazonium salt and subsequent electrochemical reactivity on gold relative to carbon was studied with some significant differences observed. The ability of the 4-sulfophenyl layer adsorbed onto gold to block access of the redox probe ferricyanide to the underlying electrodes, as determined via cyclic voltammetry was inferior to the same layers formed on glassy carbon electrodes thus indicating a more open, porous layer formed on gold. More significantly, the 4-sulfophenyl layers are shown to be far less electrochemically stable on gold than on glassy carbon. Electrochemical and X-ray photoelectron spectroscopy (XPS) evidence suggests the instability is due to cleavage of the bond between sulfonate functional group and phenyl ring. These results provide further evidence that although aryl diazonium salt layers are relatively stable on gold surfaces compared with alkanethiol based self-assembled monolayer (SAMs), the stability is not as high as is observed on carbon.7 page(s

Rev. Sci. Instrum.

Laser-generated GHz-ultrasonic-based technologies have shown the ability to image single cell adhesion and stiffness simultaneously. Using this new modality, we here demonstrate quantitative indicators to investigate contact mechanics and adhesion processes of the cell. We cultured human cells on a rigid substrate, and we used an inverted pulsed opto-acoustic microscope to generate acoustic pulses containing frequencies up to 100 GHz in the substrate. We map the reflection of the acoustic pulses at the cell-substrate interface to obtain images of the acoustic impedance of the cell, Zc, as well as of the stiffness of the interface, K, with 1 mum lateral resolution. Our results show that the standard deviation DeltaZc reveals differences between different cell types arising from the multiplicity of local conformations within the nucleus. From the distribution of K-values within the nuclear region, we extract a mean interfacial stiffness, Km, that quantifies the average contact force in areas of the cell displaying weak bonding. By analogy with classical contact mechanics, we also define the ratio of the real to nominal contact areas, Sr/St. We show that Km can be interpreted as a quantitative indicator of passive contact at metal-cell interfaces, while Sr/St is sensitive to active adhesive processes in the nuclear region. The ability to separate the contributions of passive and active adhesion processes should allow gaining insight into cell-substrate interactions, with important applications in tissue engineering.Imagerie quantitative par acoustique picoseconde de l'adhésion de cellules individuelles sur biomatériau

A Comparative study of electrochemical reduction of 4-nitrophenyl covalently grafted on gold and carbon

4-Nitrophenyl layers were grafted on gold and glassy carbon surfaces by electrochemical reductive adsorption of the corresponding diazonium salt. Electrochemical conversion efficiencies of 4-nitrophenyl moieties to 4-aminophenyl moieties on gold versus on glassy carbon in a protic medium were investigated using X-ray photoelectron spectroscopy (XPS). In total contrast to all previous comparative studies showing greater electrochemical reactivity of aryl diazonium salt-derived layers on gold than on glassy carbon, a much lower rate of conversion to 4-aminophenyl was observed on gold than on glassy carbon by both cyclic voltammetry (CV) and chronoamperometry (CA) methods. The lower electron transfer rate during conversion observed on gold versus glassy carbon was proposed to be due to a mechanism related to the molecular structure rearrangement of 4-nitrophenyl during the process on glassy carbon. However, whilst complete conversion of 4-nitrophenyl to 4-aminophenyl on gold by chronoamperometry was achieved, on glassy carbon complete reduction could not be achieved under the same conditions.7 page(s