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To test the biocompatiblecharacter of room-temperature ionic liquids(ILs), the interaction of various ILs with biological membrane (biomembrane)models was studied in this work. Dioleoyl phosphatidylcholine (DOPC)adsorbed on a mercury (Hg) electrode forms an impermeable defect-freemonolayer which is a well established biomembrane model, prone tobe studied by electrochemical techniques. We have monitored the modificationsof the Hg supported monolayer caused by ILs using rapid cyclic voltammetry(RCV), alternating current voltammetry (ACV), and electrochemicalimpedance spectroscopy (EIS). A series of imidazolium-based ILs wereinvestigated whose interaction highlighted the role of anion and lateralside chain of cation during the interaction with DOPC monolayers.It was shown that the hydrophobic and lipophilic character of theIL cations is a primary factor responsible for this interaction. Hg-supportedmonolayers provide an accurate analysis of the behavior of ILs atthe interface of a biomembrane leading to a comprehensive understandingof the interaction mechanisms involved. At the same time, these experimentsshow that the Hg-phospholipid model is an effective toxicity sensingtechnique as shown by the correlation between literature in vivo toxicitydata and the data from this study. [ABSTRACT FROM AUTHOR]

Macrophages are involved in every stage of the innate/inflammatory immune responses in the body tissues, including the resolution of the reaction, and they do so in close collaboration with the extracellular matrix (ECM). Simplified substrates with nanotopographical features attempt to mimic the structural properties of the ECM to clarify the functional features of the interaction of the ECM with macrophages. We still have a limited understanding of the macrophage behavior upon interaction with disordered nanotopography, especially with features smaller than 10 nm. Here, we combine atomic force microscopy (AFM), finite element modeling (FEM), and quantitative biochemical approaches in order to understand the mechanotransduction from the nanostructured surface into cellular responses. AFM experiments show a decrease of macrophage stiffness, measured with the Young's modulus, as a biomechanical response to a nanostructured (ns-) ZrO x surface. FEM experiments suggest that ZrO x surfaces with increasing roughness represent weaker mechanical boundary conditions. The mechanical cues from the substrate are transduced into the cell through the formation of integrin-regulated focal adhesions and cytoskeletal reorganization, which, in turn, modulate cell biomechanics by downregulating cell stiffness. Surface nanotopography and consequent biomechanical response impact the overall behavior of macrophages by increasing movement and phagocytic ability without significantly influencing their inflammatory behavior. Our study suggests a strong potential of surface nanotopography for the regulation of macrophage functions, which implies a prospective application relative to coating technology for biomedical devices.

Direct neuronal reprogramming of somatic cells into induced neurons (iNs) has been recently established as a promising approach to generating neuron cells. Previous studies have reported that the biophysical cues of the in vitro microenvironment are potent modulators in the cell fate decision; thus, the present study explores the effects of a customized pattern (named colloidal self-assembled patterns, cSAPs) on iN generation from human fibroblasts using small molecules. The result revealed that the cSAP, composed of binary particles in a hexagonal-close-packed (hcp) geometry, is capable of improving neuronal reprogramming efficiency and steering the ratio of the iN subtypes. Cells exhibited distinct cell morphology, upregulated cell adhesion markers (i.e., SDC1 and ITGAV), enriched signaling pathways (i.e., Hippo and Wnt), and chromatin remodeling on the cSAP compared to those on the control substrates. The result also showed that the iN subtype specification on cSAP was surface-dependent; therefore, the defined physicochemical cue from each cSAP is exclusive. Our findings show that direct cell reprogramming can be manipulated through specific biophysical cues on the artificial matrix, which is significant in cell transdifferentiation and lineage conversion.

Atomic force microscopy (AFM) indentation is a popular method for characterizing the micromechanical properties of soft materials such as living cells. However, the mechanical data obtained from deep indentation measurements can be difficult and problematic to interpret as a result of the complex geometry of a cell, the nonlinearity of indentation contact, and constitutive relations of heterogeneous hyperelastic soft components. Living MDA-MB-231 cells were indented by spherical probes to obtain morphological and mechanical data that were adopted to build an accurate finite element model (FEM) for a parametric study. Initially, a 2D-axisymmetric numerical model was constructed with the main purpose of understanding the effect of geometrical and mechanical properties of constitutive parts such as the cell body, nucleus, and lamellipodium. A series of FEM deformation fields were directly compared with atomic force spectroscopy in order to resolve the mechanical convolution of heterogeneous parts and quantify Young's modulus and the geometry of nuclei. Furthermore, a 3D finite element model was constructed to investigate indentation events located far from the axisymmetric geometry. In this framework, the joint FEM/AFM approach has provided a useful methodology and a comprehensive characterization of the heterogeneous structure of living cells, emphasizing the deconvolution of geometrical structure and the true elastic modulus of the cell nucleus.

The study of the toxicity, biocompatibility, and environmental sustainability of room-temperature ionic liquids (ILs) is still in its infancy. Understanding the impact of ILs on living organisms, especially from the aquatic ecosystem, is urgent, since large amounts of these substances are starting to be employed as solvents in industrial chemical processes, and on the other side, evidence of toxic effects of ILs on microorganisms and single cells have been observed. To date, the toxicity of ILs has been investigated by means of macroscopic assays aimed at characterizing the effective concentrations (like the EC 50 ) that cause the death of a significant fraction of the population of microorganisms and cells. These studies allow us to identify the cell membrane as the first target of the IL interaction, whose effectiveness was correlated to the lipophilicity of the cation, i.e., to the length of the lateral alkyl chain. Our study aimed at investigating the molecular mechanisms underpinning the interaction of ILs with living cells. To this purpose, we carried out a combined topographic and mechanical analysis by atomic force microscopy of living breast metastatic cancer cells (MDA-MB-231) upon interaction with imidazolium-based ILs. We showed that ILs are able to induce modifications of the overall rigidity (effective Young's modulus) and morphology of the cells. Our results demonstrate that ILs act on the physical properties of the outer cell layer (the membrane linked to the actin cytoskeleton), already at concentrations below the EC 50 . These potentially toxic effects are stronger at higher IL concentrations, as well as with longer lateral chains in the cation.

Here, we present the first observation of magneto-transport properties of graphene foam (GF) composed of a few layers in a wide temperature range of 2-300 K. Large room-temperature linear positive magnetoresistance (PMR ≈ 171% at B ≈ 9 T) has been detected. The largest PMR (∼213%) has been achieved at 2 K under a magnetic field of 9 T, which can be tuned by the addition of poly(methyl methacrylate) to the porous structure of the foam. This remarkable magnetoresistance may be the result of quadratic magnetoresistance. The excellent magneto-transport properties of GF open a way toward three-dimensional graphene-based magnetoelectronic devices.

Phospholipid monolayers on mercury (Hg) surfaces have received substantial and extensive scientific interest not only because of their use as a biomembrane model but also for their application as a successful toxicity-sensing element. The monolayers show characteristic and very reproducible phase transitions manifest as consecutive voltammetric peaks in response to applied transverse electric fields. Unfortunately, apart from the results of simulation studies, there is a lack of data on the lipid phase structures to help interpret these voltammetric peaks. In this paper we report on the direct measurement of the structural changes underlying the phase transitions of phospholipid layers of dioleoyl phosphatidylcholine (DOPC) at electrified Hg surfaces using atomic force microscopy force-distance techniques. These direct measurements enable a description of the following structural changes in fluid lipid assemblies on a liquid electrode within an increasing transverse electric field. At about -1.0 V (vs Ag/AgCl) a field-facilitated ingress of ions and water into the monolayer results in a phase transition to a structured 2D emulsion. This is followed by a further phase transition at more negative potentials involving the readsorption of bilayer patches. At stronger values of field the bilayer patches form semivesicles, which subsequently collapse to form a monolayer of uncertain composition at very negative potentials. The observation that a monolayer on Hg converts to a bilayer by increasing the applied potential has allowed techniques to be developed for preparing and characterizing a near-continuous DOPC bilayer on Hg in an applied potential window within -1.0 and -1.4 V (vs Ag/AgCl).