Cells have evolved multiple mechanisms to apprehend and adapt finely to their environment. Here we report a new cellular ability, which we term "curvotaxis" that enables the cells to respond to ...cell-scale curvature variations, a ubiquitous trait of cellular biotopes. We develop ultra-smooth sinusoidal surfaces presenting modulations of curvature in all directions, and monitor cell behavior on these topographic landscapes. We show that adherent cells avoid convex regions during their migration and position themselves in concave valleys. Live imaging combined with functional analysis shows that curvotaxis relies on a dynamic interplay between the nucleus and the cytoskeleton-the nucleus acting as a mechanical sensor that leads the migrating cell toward concave curvatures. Further analyses show that substratum curvature affects focal adhesions organization and dynamics, nuclear shape, and gene expression. Altogether, this work identifies curvotaxis as a new cellular guiding mechanism and promotes cell-scale curvature as an essential physical cue.
The need to control the adhesion of cells to material surfaces plays an important role in determining the design of biomaterial substrates for biotechnology and tissue-engineering applications. As a ...the first step in a cascade of cellular events, adhesion affects many aspects of cell
function, including spreading, migration, proliferation and differentiation. After a short description of cell adhesion and essential molecules involved in, the present knowledge on the influence of surface topography on cell behavior will be described by considering not only the amplitude
of the surface topography but also its organization at all scales (micro- and nano-scale). The biological mechanisms underlying the cell response to topography will be evoked. Secondly, the influence of surface chemistry as well as surface energy on cell adhesion will be described. Thirdly,
as the cells never interact with a bare material but with materials on which the proteins from biological fluids have adsorbed, some studies on the role of proteins in cell adhesion will be used to illustrate this point. Finally, the influence of substrate mechanics on cell differentiation
will be described.
The proper integration of biophysical cues from the cell vicinity is crucial for cells to maintain homeostasis, cooperate with other cells within the tissues, and properly fulfill their biological ...function. It is therefore crucial to fully understand how cells integrate these extracellular signals for tissue engineering and regenerative medicine. Topography has emerged as a prominent component of the cellular microenvironment that has pleiotropic effects on cell behavior. This progress report focuses on the recent advances in the understanding of the topography sensing mechanism with a special emphasis on the role of the nucleus. Here, recent techniques developed for monitoring the nuclear mechanics are reviewed and the impact of various topographies and their consequences on nuclear organization, gene regulation, and stem cell fate is summarized. The role of the cell nucleus as a sensor of cell‐scale topography is further discussed.
Topography is a prominent component of the cellular microenvironment. The discovery of the role of the nucleus in the cellular response to topography has been demonstrated very recently. This progress report outlines the recent knowledge in the topography sensing mechanism with a special emphasis on the role of the cell nucleus as a sensor of cell‐scale topography.
Evolution of the chemical properties of oxygen or nitrogen plasma treated polystyrene surfaces over extended time of storage.
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•Cold plasma treatment induces strong modifications of ...the surface chemistry.•XPS characterization of polystyrene dishes is evaluated after plasma treatment.•Surface characterization exhibits initial chemical instability period of two weeks.•Nitrogen plasma treated surfaces exhibit oxidation over a period of 600 days.•Oxygen plasma treated surfaces are chemically stable over the same period.
A polystyrene surface (PS) was initially treated by cold nitrogen and oxygen plasma in order to incorporate in particular amine and hydroxyl functions, respectively. The evolution of the chemical nature of the surface was further monitored over a long time period (580 days) by chemical assay, XPS and contact angle measurements. Surface density quantification of primary amine groups was performed using three chemical amine assays: 4-nitrobenzaldehyde (4-NBZ), Sulfo succinimidyl 6-3′(2 pyridyldithio)-pionamido hexanoate (Sulfo-LC-SPDP) and iminothiolane (ITL). The results showed amine densities were in the range of 2 per square nanometer (comparable to the results described in the literature) after 5min of nitrogen plasma treatment. Over the time period investigated, chemical assays, XPS and contact angles suggest a drastic significant evolution of the chemical nature of the surface within the first two weeks. Beyond that time period and up to almost two years, nitrogen plasma modified substrates exhibits a slow and continuous oxidation whereas oxygen plasma modifed polystyrene surface is chemically stable after two weeks of storage. The latter appeared to “ease of” showing relatively mild changes within the one year period.
Our results suggest that it may be preferable to wait for a chemical “stabilization” period of two weeks before subsequent covalent immobilization of proteins onto the surface. The originality of this work resides in the study of the plasma treated surface chemistry evolution over long periods of storage time (580 days) considerably exceeding those described in the literature.
How biophysical cues can control tissue morphogenesis is a central question in biology and for the development of efficient tissue engineering strategies. Recent data suggest that specific ...topographies such as grooves and ridges can trigger anisotropic tissue growth. However, the specific contribution of biologically relevant topographical features such as cell-scale curvature is still unclear. Here we engineer a series of grooves and ridges model topographies exhibiting specific curvature at the ridge/groove junctions and monitored the growth of epithelial colonies on these surfaces. We observe a striking proportionality between the maximum convex curvature of the ridges and the elongation of the epithelium. This is accompanied by the anisotropic distribution of F-actin and nuclei with partial exclusion of both in convex regions as well as the curvature-dependent reorientation of pluricellular protrusions and mitotic spindles. This demonstrates that curvature itself is sufficient to trigger and modulate the oriented growth of epithelia through the formation of convex "topographical barriers" and establishes curvature as a powerful tuning parameter for tissue engineering and biomimetic biomaterial design.
Increased life expectancy in industrialized countries is causing an increased incidence of osteoporosis and the need for bioactive bone implants. The integration of implants can be improved ...physically, but mainly by chemical modifications of the material surface. It was recognized that amino-group-containing coatings improved cell attachment and intracellular signaling. The aim of this study was to determine the role of the amino group density in this positive cell behavior by developing controlled amino-rich nanolayers. This work used covalent grafting of polymer-based nanocoatings with different amino group densities. Titanium coated with the positively-charged trimethoxysilylpropyl modified poly(ethyleneimine) (Ti-TMS-PEI), which mostly improved cell area after 30 min, possessed the highest amino group density with an N/C of 32%. Interestingly, changes in adhesion-related genes on Ti-TMS-PEI could be seen after 4 h. The mRNA microarray data showed a premature transition of the MG-63 cells into the beginning differentiation phase after 24 h indicating Ti-TMS-PEI as a supportive factor for osseointegration. This amino-rich nanolayer also induced higher bovine serum albumin protein adsorption and caused the cells to migrate slower on the surface after a more extended period of cell settlement as an indication of a better surface anchorage. In conclusion, the cell spreading on amine-based nanocoatings correlated well with the amino group density (N/C).
Most of the implant-associated infections are attributed to bacteria adhering to biomaterial surfaces as "biofilm" communities. Bacterial transport, first contact with the surface as well as some of ...the further developments can be considered and can be described using physical-chemical
concepts. However, far from simple colloidal particles, bacteria have various macromolecular structures at their cell wall surface for interacting with their surroundings through specific and non-specific bindings. They are also able to modify composition and features of their cell wall in
response to specific surrounding conditions. Therefore, bacteria/surface material interface is a complex topic, involving chemical and physical-chemical characteristics of both material surface and bacterial cell wall, as well as biological characteristics of bacteria. Furthermore, proteins
and other biomolecules coming from surrounding medium influence the bacteria/material interface by adsorbing onto the material surface prior to any adhesion of bacteria. Finally, bacterial adhesion and biofilm formation phenomena occur at the same time as eukaryotic cell adhesion in an acute
competition for adhering to and colonising the biomaterial surface. Therefore, developing biomaterials able to favour cell adhesion without promoting also bacterial adhesion appears still to be a challenge. In this article, we describe briefly the common development and particularities
of biofilms before focusing on what for and whether bacterial features and material surface properties are likely to be involved in bacterial adhesion, the first step in biofilm formation. The influence of adsorbed biomolecules at the bacteria/material interface is finally addressed, as well
as the current knowledge about the competition between bacteria and eukaryotic cells.
Functional coatings based on the assembly of submicrometric or nanoparticles are found in many applications in the biomedical field. However, these nanoparticle-based coatings are particularly ...fragile since they could be exposed to cells that are able to internalize nanoparticles. Here, we studied the efficiency of RAW 264.7 murine macrophages to internalize physisorbed silica nanoparticles as a function of time and particle size. This cell internalization efficiency was evaluated from the damages induced by the cells in the nanoparticle-based monolayer on the basis of scanning electron microscopy and confocal laser scanning microscopy observations. The internalization efficiency in terms of the percentage of nanoparticles cleared from the substrate is characterized by two size-dependent regimes. Additionally, we highlighted that a delay before internalization occurs, which increases with decreasing adsorbed nanoparticle size. This internalization is characterized by a minimal threshold that corresponds to 35 nm nanoparticles that are not internalized during the 12-h incubation considered in this work.
Human mesenchymal stem (hMSCs) are defined as multi-potent colony-forming cells expressing a specific subset of plasma membrane markers when grown on flat tissue culture polystyrene. However, as soon ...as hMSCs are used for transplantation, they are exposed to a 3D environment, which can strongly impact cell physiology and influence proliferation, differentiation and metabolism. Strategies to control in vivo hMSC behavior, for instance in stem cell transplantation or cancer treatment, are skewed by the un-physiological flatness of the standard well plates. Even though it is common knowledge that cells behave differently in vitro compared to in vivo, only little is known about the underlying adaptation processes. Here, we used micrometer-scale defined surface topographies as a model to describe the phenotype of hMSCs during this adaptation to their new environment. We used well established techniques to compare hMSCs cultured on flat and topographically enhanced polystyreneand observed dramatically changed cell morphologies accompanied by shrinkage of cytoplasm and nucleus, a decreased overall cellular metabolism, and slower cell cycle progression resulting in a lower proliferation rate in cells exposed to surface topographies. We hypothesized that this reduction in proliferation rate effects their sensitivity to certain cancer drugs, which was confirmed by higher survival rate of hMSCs cultured on topographies exposed to paclitaxel. Thus, micro-topographies can be used as a model system to mimic the natural cell micro-environment, and be a powerful tool to optimize cell treatment in vitro.
Bone is a specialized tissue formed by different cell types and a multiscale, complex mineralized matrix. The architecture and the surface chemistry of this microenvironment can be factors of ...considerable influence on cell biology, and can affect cell proliferation, commitment to differentiation, gene expression, matrix production and/or composition. It has been shown that osteoblasts encounter natural motifs in vivo, with various topographies (shapes, sizes, organization), and that cell cultures on flat surfaces do not reflect the total potential of the tissue. Therefore, studies investigating the role of topographies on cell behavior are important in order to better understand the interaction between cells and surfaces, to improve osseointegration processes in vivo between tissues and biomaterials, and to find a better topographic surface to enhance bone repair. In this review, we evaluate the main available data about surface topographies, techniques for topographies’ production, mechanical signal transduction from surfaces to cells and the impact of cell–surface interactions on osteoblasts or preosteoblasts’ behavior.
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