Dynamic Regulation of Cell Mechanotransduction through Sequentially Controlled Mobile Surfaces.

The physical properties of nanoscale cell-extracellular matrix (ECM) ligands profoundly impact biological processes, such as adhesion, motility, and differentiation. While the mechanoresponse of cells to static ligands is well-studied, the effect of dynamic ligand presentation with "adaptive" properties on cell mechanotransduction remains less understood. Utilizing a controllable diffusible ligand interface, we demonstrated that cells on surfaces with rapid ligand mobility could recruit ligands through activating integrin α5ß1, leading to faster focal adhesion growth and spreading at the early adhesion stage. By leveraging UV-light-sensitive anchor molecules to trigger a "dynamic to static" transformation of ligands, we sequentially activated α5ß1 and αvß3 integrins, significantly promoting osteogenic differentiation of mesenchymal stem cells. This study illustrates how manipulating molecular dynamics can directly influence stem cell fate, suggesting the potential of "sequentially" controlled mobile surfaces as adaptable platforms for engineering smart biomaterial coatings.

Stability Study of Synthetic Diamond Using a Thermally Controlled Biological Environment: Application towards Long-Lasting Neural Prostheses.

This paper demonstrates, for the first time, the stability of synthetic diamond as a passive layer within neural implants. Leveraging the exceptional biocompatibility of intrinsic nanocrystalline diamond, a comprehensive review of material aging analysis in the context of in-vivo implants is provided. This work is based on electric impedance monitoring through the formulation of an analytical model that scrutinizes essential parameters such as the deposited metal resistivity, insulation between conductors, changes in electrode geometry, and leakage currents. The evolution of these parameters takes place over an equivalent period of approximately 10 years. The analytical model, focusing on a fractional capacitor, provides nuanced insights into the surface conductivity variation. A comparative study is performed between a classical polymer material (SU8) and synthetic diamond. Samples subjected to dynamic impedance analysis reveal distinctive patterns over time, characterized by their physical degradation. The results highlight the very high stability of diamond, suggesting promise for the electrode's enduring viability. To support this analysis, microscopic and optical measurements conclude the paper and confirm the high stability of diamond and its strong potential as a material for neural implants with long-life use.

Adsorption of Ferritin at Nanofaceted Al2O3 Surfaces.

The influence of nanoscale surface topography on protein adsorption is highly important for numerous applications in medicine and technology. Herein, ferritin adsorption at flat and nanofaceted, single-crystalline Al2O3 surfaces is investigated using atomic force microscopy and X-ray photoelectron spectroscopy. The nanofaceted surfaces are generated by the thermal annealing of Al2O3 wafers at temperatures above 1000 °C, which leads to the formation of faceted saw-tooth-like surface topographies with periodicities of about 160 nm and amplitudes of about 15 nm. Ferritin adsorption at these nanofaceted surfaces is notably suppressed compared to the flat surface at a concentration of 10 mg/mL, which is attributed to lower adsorption affinities of the newly formed facets. Consequently, adsorption is restricted mostly to the pattern grooves, where the proteins can maximize their contact area with the surface. However, this effect depends on the protein concentration, with an inverse trend being observed at 30 mg/mL. Furthermore, different ferritin adsorption behavior is observed at topographically similar nanofacet patterns fabricated at different annealing temperatures and attributed to different step and kink densities. These results demonstrate that while protein adsorption at solid surfaces can be notably affected by nanofacet patterns, fine-tuning protein adsorption in this way requires the precise control of facet properties.

Multiprotein Adsorption from Human Serum at Gold and Oxidized Iron Surfaces Studied by Atomic Force Microscopy and Polarization-Modulation Infrared Reflection Absorption Spectroscopy.

Multiprotein adsorption from complex body fluids represents a highly important and complicated phenomenon in medicine. In this work, multiprotein adsorption from diluted human serum at gold and oxidized iron surfaces is investigated at different serum concentrations and pH values. Adsorption-induced changes in surface topography and the total amount of adsorbed proteins are quantified by atomic force microscopy (AFM) and polarization-modulation infrared reflection absorption spectroscopy (PM-IRRAS), respectively. For both surfaces, stronger protein adsorption is observed at pH 6 compared to pH 7 and pH 8. PM-IRRAS furthermore provides some qualitative insights into the pH-dependent alterations in the composition of the adsorbed multiprotein films. Changes in the amide II/amide I band area ratio and in particular side-chain IR absorption suggest that the increased adsorption at pH 6 is accompanied by a change in protein film composition. Presumably, this is mostly driven by the adsorption of human serum albumin, which at pH 6 adsorbs more readily and thereby replaces other proteins with lower surface affinities in the resulting multiprotein film.

Multiscale simulation analysis of passive and active micro/nanoelectrodes for CMOS-based in vitro neural sensing devices.

Neuron and neural network studies are remarkably fostered by novel stimulation and recording systems, which often make use of biochips fabricated with advanced electronic technologies and, notably, micro- and nanoscale complementary metal-oxide semiconductor (CMOS). Models of the transduction mechanisms involved in the sensor and recording of the neuron activity are useful to optimize the sensing device architecture and its coupling to the readout circuits, as well as to interpret the measured data. Starting with an overview of recently published integrated active and passive micro/nanoelectrode sensing devices for in vitro studies fabricated with modern (CMOS-based) micro-nano technology, this paper presents a mixed-mode device-circuit numerical-analytical multiscale and multiphysics simulation methodology to describe the neuron-sensor coupling, suitable to derive useful design guidelines. A few representative structures and coupling conditions are analysed in more detail in terms of the most relevant electrical figures of merit including signal-to-noise ratio. This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.

New Poly(N-isopropylacrylamide-butylacrylate) Copolymer Biointerfaces and Their Characteristic Influence on Cell Behavior In Vitro.

Designing and obtaining new synthetic smart biointerfaces with specific and controlled characteristics relevant for applications in biomedical and bioengineering domains represents one of the main challenges in these fields. In this work, Matrix-Assisted Pulsed Laser Evaporation (MAPLE) is used to obtain synthetic biointerfaces of poly(N-isopropyl acrylamide-butyl acrylate) p(NIPAM-BA) copolymer with different characteristics (i.e., roughness, porosity, wettability), and their effect on normal HEK 293 T and murine melanoma B16-F1 cells is studied. For this, the influence of various solvents (chloroform, dimethylsulfoxide, water) and fluence variation (250-450 mJ/cm2) on the morphological, roughness, wettability, and physico-chemical characteristics of the coatings are evaluated by atomic force microscopy, scanning electron microscopy, contact angle measurements, Fourier-transform-IR spectroscopy, and X-ray photoelectron spectroscopy. Coatings obtained by the spin coating method are used for reference. No significant alteration in the chemistry of the surfaces is observed for the coatings obtained by both methods. All p(NIPAM-BA) coatings show hydrophilic character, with the exception of those obtained with chloroform at 250 mJ/cm2. The surface morphology is shown to depend on both solvent type and laser fluence and it ranges from smooth surfaces to rough and porous ones. Physico-chemical and biological analysis reveal that the MAPLE deposition method with fluences of 350-450 mJ/cm2 when using DMSO solvent is more appropriate for bioengineering applications due to the surface characteristics (i.e., pore presence) and to the good compatibility with normal cells and cytotoxicity against melanoma cells.

Nano- and Microscale Optical and Electrical Biointerfaces and Their Relevance to Energy Research.

Different research fields in energy sciences, such as photovoltaics for solar energy conversion, supercapacitors for energy storage, electrocatalysis for clean energy conversion technologies, and materials-bacterial hybrid for CO2 fixation have been under intense investigations over the past decade. In recent years, new platforms for biointerface designs have emerged from the energy conversion and storage principles. This paper reviews recent advances in nano- and microscale materials/devices for optical and electrical biointerfaces. First, a connection is drawn between biointerfaces and energy science, and how these two distinct research fields can be connected is summarized. Then, a brief overview of current available tools for biointerface studies is presented. Third, three representative biointerfaces are reviewed, including neural, cardiac, and bacterial biointerfaces, to show how to apply these tools and principles to biointerface design and research. Finally, two possible future research directions for nano- and microscale biointerfaces are proposed.

Surface Design for Immobilization of an Antimicrobial Peptide Mimic for Efficient Anti-Biofouling.

Microbial surface attachment negatively impacts a wide range of devices from water purification membranes to biomedical implants. Mimics of antimicrobial peptides (AMPs) constituted from poly(N-substituted glycine) "peptoids" are of great interest as they resist proteolysis and can inhibit a wide spectrum of microbes. We investigate how terminal modification of a peptoid AMP-mimic and its surface immobilization affect antimicrobial activity. We also demonstrate a convenient surface modification strategy for enabling alkyne-azide "click" coupling on amino-functionalized surfaces. Our results verified that the N- and C-terminal peptoid structures are not required for antimicrobial activity. Moreover, our peptoid immobilization density and choice of PEG tether resulted in a "volumetric" spatial separation between AMPs that, compared to past studies, enabled the highest AMP surface activity relative to bacterial attachment. Our analysis suggests the importance of spatial flexibility for membrane activity and that AMP separation may be a controlling parameter for optimizing surface anti-biofouling.

Osseointegration mechanisms: a proteomic approach.

The prime objectives in the development of biomaterials for dental applications are to improve the quality of osseointegration and to short the time needed to achieve it. Design of implants nowadays involves changes in the surface characteristics to obtain a good cellular response. Incorporating osteoinductive elements is one way to achieve the best regeneration possible post-implantation. This study examined the osteointegrative potential of two distinct biomaterials: sandblasted acid-etched titanium and a silica sol-gel hybrid coating, 70% MTMOS-30% TEOS. In vitro, in vivo, and proteomic characterisations of the two materials were conducted. Enhanced expression levels of ALP and IL-6 in the MC3T3-E1 cells cultured with coated discs, suggest that growing cells on such surfaces may increase mineralisation levels. 70M30T-coated implants showed improved bone growth in vivo compared to uncoated titanium. Complete osseointegration was achieved on both. However, coated implants displayed osteoinductive properties, while uncoated implants demonstrated osteoconductive characteristics. Coagulation-related proteins attached predominantly to SAE-Ti surface. Surface properties of the material might drive the regenerative process of the affected tissue. Analysis of the proteins on the coated dental implant showed that few proteins specifically attached to its surface, possibly indicating that its osteoinductive properties depend on the silicon delivery from the implant.

Chemical Design of Non-Ionic Polymer Brushes as Biointerfaces: Poly(2-oxazine)s Outperform Both Poly(2-oxazoline)s and PEG.

The era of poly(ethylene glycol) (PEG) brushes as a universal panacea for preventing non-specific protein adsorption and providing lubrication to surfaces is coming to an end. In the functionalization of medical devices and implants, in addition to preventing non-specific protein adsorption and cell adhesion, polymer-brush formulations are often required to generate highly lubricious films. Poly(2-alkyl-2-oxazoline) (PAOXA) brushes meet these requirements, and depending on their side-group composition, they can form films that match, and in some cases surpass, the bioinert and lubricious properties of PEG analogues. Poly(2-methyl-2-oxazine) (PMOZI) provides an additional enhancement of brush hydration and main-chain flexibility, leading to complete bioinertness and a further reduction in friction. These data redefine the combination of structural parameters necessary to design polymer-brush-based biointerfaces, identifying a novel, superior polymer formulation.

Flexible Gold Nanocone Array Surfaces as a Tool for Regulating Neuronal Behavior.

Accelerated neurite outgrowth of rat cortical neurons on a flexible and inexpensive substrate functionalized with gold nanocone arrays is reported. The gold nanocone arrays are fabricated on Teflon films by a bottom-up approach based on colloidal lithography followed by deposition of a thin gold layer. The geometry of nanocone arrays including height and pitch is controlled by the overall etching time and template polystyrene beads size. Fluorescence microscopy studies reveal high viability and significant morphological changes of the neurons on the structured surfaces. The elongation degree of neurite is maximized on the nanocone arrays created with 1 µm polystyrene beads by a factor of two with respect to the control. Furthermore, the interface between the neurons and the nanocones is investigated by scanning electron microscopy and focused ion beam cross-sectioning. The detailed observation of the neuron/nanocone interfaces reveals the morphological similarity between the nanocone tips and the neuronal processes, the existence of interspace at the interface between the cell body and the nanocones, and neurite bridging among the neighboring structures, which may induce the acceleration of neurite outgrowth. The flexible gold nanocone arrays can be a good supporting substrate of neuron culture with noble electrical and optical properties.

Smart Polymers with Special Wettability.

Surface wettability plays a key role in addressing issues ranging from basic life activities to our daily life, and thus being able to control it is an attractive goal. Learning from nature, both of its structure and function, brings us much inspiration in designing smart polymers to tackle this major challenge. Life functions particularly depend on biomolecular recognition-induced interfacial properties from the aqueous phase onto either "soft" cell and tissue or "hard" inorganic bone and tooth surfaces. The driving force is noncovalent weak interactions rather than strong covalent combinations. An overview is provided of the weak interactions that perform vital actions in mediating biological processes, which serve as a basis for elaborating multi-component polymers with special wettabilities. The role of smart polymers from molecular recognitions to macroscopic properties are highlighted. The rationale is that highly selective weak interactions are capable of creating a dynamic synergetic communication in the building components of polymers. Biomolecules could selectively induce conformational transitions of polymer chains, and then drive a switching of physicochemical properties, e.g., roughness, stiffness and compositions, which are an integrated embodiment of macroscopic surface wettabilities.

The Diverse Range of Possible Cell Membrane Interactions with Substrates: Drug Delivery, Interfaces and Mobility.

The cell membrane has gained significant attention as a platform for the development of bio-inspired nanodevices due to its immune-evasive functionalities and copious bio-analogs. This review will examine several uses of cell membranes such as (i) therapeutic delivery carriers with or without substrates (i.e., nanoparticles and artificial polymers) that have enhanced efficiency regarding copious cargo loading and controlled release, (ii) exploiting nano-bio interfaces in membrane-coated particles from the macro- to the nanoscales, which would help resolve the biomedical issues involved in biological interfacing in the body, and (iii) its effects on the mobility of bio-moieties such as lipids and/or proteins in cell membranes, as discussed from a biophysical perspective. We anticipate that this review will influence both the development of novel anti-phagocytic delivery cargo and address biophysical problems in soft and complex cell membrane.

An Epitope-Imprinted Biointerface with Dynamic Bioactivity for Modulating Cell-Biomaterial Interactions.

In this study, an epitope-imprinting strategy was employed for the dynamic display of bioactive ligands on a material interface. An imprinted surface was initially designed to exhibit specific affinity towards a short peptide (i.e., the epitope). This surface was subsequently used to anchor an epitope-tagged cell-adhesive peptide ligand (RGD: Arg-Gly-Asp). Owing to reversible epitope-binding affinity, ligand presentation and thereby cell adhesion could be controlled. As compared to current strategies for the fabrication of dynamic biointerfaces, for example, through reversible covalent or host-guest interactions, such a molecularly tunable dynamic system based on a surface-imprinting process may unlock new applications in in situ cell biology, diagnostics, and regenerative medicine.

Dynamic biointerfaces: from recognition to function.

The transformation of recognition signals into regulating macroscopic behaviors of biological entities (e.g., biomolecules and cells) is an extraordinarily challenging task in engineering interfacial properties of artificial materials. Recently, there has been extensive research for dynamic biointerfaces driven by biomimetic techniques. Weak interactions and chirality are two crucial routes that nature uses to achieve its functions, including protein folding, the DNA double helix, phospholipid membranes, photosystems, and shell and tooth growths. Learning from nature inspires us to design dynamic biointerfaces, which usually take advantage of highly selective weak interactions (e.g., synergetic chiral H-bonding interactions) to tailor their molecular assemblies on external stimuli. Biomolecules can induce the conformational transitions of dynamic biointerfaces, then drive a switching of surface characteristics (topographic structure, wettability, etc.), and eventually achieve macroscopic functions. The emerging progresses of dynamic biointerfaces are reviewed and its role from molecular recognitions to biological functions highlighted. Finally, a discussion is presented of the integration of dynamic biointerfaces with the basic biochemical processes, possibly solving the big challenges in life science.

A stable, reusable, and highly active photosynthetic bioreactor by bio-interfacing an individual cyanobacterium with a mesoporous bilayer nanoshell.

An individual cyanobacterium cell is interfaced with a nanoporous biohybrid layer within a mesoporous silica layer. The bio-interface acts as an egg membrane for cell protection and growth of outer shell. The resulting bilayer shell provides efficient functions to create a single cell photosynthetic bioreactor with high stability, reusability, and activity.

Out-of-Plane Plasmonic Antennas for Raman Analysis in Living Cells.

Out-of-plane plasmonic nanoantennas protruding from the substrate are exploited to perform very sensitive surface enhanced Raman scattering analysis of living cells. Cells cultured on three-dimensional surfaces exhibit tight adhesion with nanoantenna tips where the plasmonic hot-spot resides. This fact provides observable cell adhesion sites combined with high plasmonic enhancement, resulting in an ideal system for Raman investigation of cell membranes.

Probing multivalency in ligand-receptor-mediated adhesion of soft, biomimetic interfaces.

Many biological functions at cell level are mediated by the glycocalyx, a dense carbohydrate-presenting layer. In this layer specific interactions between carbohydrate ligands and protein receptors are formed to control cell-cell recognition, cell adhesion and related processes. The aim of this work is to shed light on the principles of complex formation between surface anchored carbohydrates and receptor surfaces by measuring the specific adhesion between surface bound mannose on a concanavalin A (ConA) layer via poly(ethylene glycol)-(PEG)-based soft colloidal probes (SCPs). Special emphasis is on the dependence of multivalent presentation and density of carbohydrate units on specific adhesion. Consequently, we first present a synthetic strategy that allows for controlled density variation of functional groups on the PEG scaffold using unsaturated carboxylic acids (crotonic acid, acrylic acid, methacrylic acid) as grafting units for mannose conjugation. We showed by a range of analytic techniques (ATR-FTIR, Raman microscopy, zeta potential and titration) that this synthetic strategy allows for straightforward variation in grafting density and grafting length enabling the controlled presentation of mannose units on the PEG network. Finally we determined the specific adhesion of PEG-network-conjugated mannose units on ConA surfaces as a function of density and grafting type. Remarkably, the results indicated the absence of a molecular-level enhancement of mannose/ConA interaction due to chelate- or subsite-binding. The results seem to support the fact that weak carbohydrate interactions at mechanically flexible interfaces hardly undergo multivalent binding but are simply mediated by the high number of ligand-receptor interactions.

Designing fractal nanostructured biointerfaces for biomedical applications.

Fractal structures in nature offer a unique "fractal contact mode" that guarantees the efficient working of an organism with an optimized style. Fractal nanostructured biointerfaces have shown great potential for the ultrasensitive detection of disease-relevant biomarkers from small biomolecules on the nanoscale to cancer cells on the microscale. This review will present the advantages of fractal nanostructures, the basic concept of designing fractal nanostructured biointerfaces, and their biomedical applications for the ultrasensitive detection of various disease-relevant biomarkers, such microRNA, cancer antigen 125, and breast cancer cells, from unpurified cell lysates and the blood of patients.

Liquid Metal-Enabled Epidermal Interfaces.

Soft materials are crucial for epidermal interfaces in biomedical devices due to their capability to conform to the body compared to rigid inorganic materials. Gels, liquids, and polymers have been extensively explored, but they lack sufficient electrical and thermal conductivity required for many application settings. Gallium-based alloys are molten metals at room temperature with exceptional electrical and thermal conductivity. These liquid metals and their composites can be directly applied onto the skin as interface materials. In this Spotlight on Applications, we focus on the rapidly evolving field of liquid metal-enabled epidermal interfaces featuring unique physical properties beyond traditional gels and polymers. We delve into the role of liquid metal in electrical and thermal biointerfaces in various epidermal applications. Current challenges and future directions in this active area are also discussed.