Single-Polymer Friction Force Microscopy of dsDNA Interacting with a Nanoporous Membrane.

Surface-grafted polymers can reduce friction between solids in liquids by compensating the normal load with osmotic pressure, but they can also contribute to friction when fluctuating polymers entangle with the sliding counter face. We have measured forces acting on a single fluctuating double-stranded DNA polymer, which is attached to the tip of an atomic force microscope and interacts intermittently with nanometer-scale methylated pores of a self-assembled polystyrene-block-poly(4-vinylpyridine) membrane. Rare binding of the polymer into the pores is followed by a stretching of the polymer between the laterally moving tip and the surface and by a force-induced detachment. We present results for the velocity dependence of detachment forces and of attachment frequency and discuss them in terms of rare excursions of the polymer beyond its equilibrium configuration.

Revealing the Meissner Corpuscles in Human Glabrous Skin Using In Vivo Non-Invasive Imaging Techniques.

The presence of mechanoreceptors in glabrous skin allows humans to discriminate textures by touch. The amount and distribution of these receptors defines our tactile sensitivity and can be affected by diseases such as diabetes, HIV-related pathologies, and hereditary neuropathies. The quantification of mechanoreceptors as clinical markers by biopsy is an invasive method of diagnosis. We report the localization and quantification of Meissner corpuscles in glabrous skin using in vivo, non-invasive optical microscopy techniques. Our approach is supported by the discovery of epidermal protrusions which are co-localized with Meissner corpuscles. Index fingers, small fingers, and tenar palm regions of ten participants were imaged by optical coherence tomography (OCT) and laser scan microscopy (LSM) to determine the thickness of the stratum corneum and epidermis and to count the Meissner corpuscles. We discovered that regions containing Meissner corpuscles could be easily identified by LSM with an enhanced optical reflectance above the corpuscles, caused by a protrusion of the strongly reflecting epidermis into the stratum corneum with its weak reflectance. We suggest that this local morphology above Meissner corpuscles has a function in tactile perception.

Human glabrous skin contains crystallized urea dendriform structures in the stratum corneum which affect the hydration levels.

Glabrous skin is hair-free skin with a high density of sweat glands, which is found on the palms, and soles of mammalians, covered with a thick stratum corneum. Dry hands are often an occupational problem which deserves attention from dermatologists. Urea is found in the skin as a component of the natural moisturizing factor and of sweat. We report the discovery of dendrimer structures of crystalized urea in the stratum corneum of palmar glabrous skin using laser scanning microscopy. The chemical and structural nature of the urea crystallites was investigated in vivo by non-invasive techniques. The relation of crystallization to skin hydration was explored. We analysed the index finger, small finger and tenar palmar area of 18 study participants using non-invasive optical methods, such as laser scanning microscopy, Raman microspectroscopy and two-photon tomography. Skin hydration was measured using corneometry. Crystalline urea structures were found in the stratum corneum of about two-thirds of the participants. Participants with a higher density of crystallized urea structures exhibited a lower skin hydration. The chemical nature and the crystalline structure of the urea were confirmed by Raman microspectroscopy and by second harmonic generated signals in two-photon tomography. The presence of urea dendrimer crystals in the glabrous skin seems to reduce the water binding capacity leading to dry hands. These findings highlight a new direction in understanding the mechanisms leading to dry hands and open opportunities for the development of better moisturizers and hand disinfection products and for diagnostic of dry skin.

Nanoscale friction on MoS2/graphene heterostructures.

Stacked hetero-structures of two-dimensional materials allow for a design of interactions with corresponding electronic and mechanical properties. We report structure, work function, and frictional properties of 1 to 4 layers of MoS2 grown by chemical vapor deposition on epitaxial graphene on SiC(0001). Experiments were performed by atomic force microscopy in ultra-high vacuum. Friction is dominated by adhesion which is mediated by a deformation of the layers to adapt the shape of the tip apex. Friction decreases with increasing number of MoS2 layers as the bending rigidity leads to less deformation. The dependence of friction on applied load and bias voltage can be attributed to variations in the atomic potential corrugation of the interface, which is enhanced by both load and applied bias. Minimal friction is obtained when work function differences are compensated.

Molecular stiffness cues of an interpenetrating network hydrogel for cell adhesion.

Understanding cells' response to the macroscopic and nanoscale properties of biomaterials requires studies in model systems with the possibility to tailor their mechanical properties and different length scales. Here, we describe an interpenetrating network (IPN) design based on a stiff PEGDA host network interlaced within a soft 4-arm PEG-Maleimide/thiol (guest) network. We quantify the nano- and bulk mechanical behavior of the IPN and the single network hydrogels by single-molecule force spectroscopy and rheological measurements. The IPN presents different mechanical cues at the molecular scale, depending on which network is linked to the probe, but the same mechanical properties at the macroscopic length scale as the individual host network. Cells attached to the interpenetrating (guest) network of the IPN or to the single network (SN) PEGDA hydrogel modified with RGD adhesive ligands showed comparable attachment and spreading areas, but cells attached to the guest network of the IPN, with lower molecular stiffness, showed a larger number and size of focal adhesion complexes and a higher concentration of the Hippo pathway effector Yes-associated protein (YAP) than cells linked to the PEGDA single network. The observations indicate that cell adhesion to the IPN hydrogel through the network with lower molecular stiffness proceeds effectively as if a higher ligand density is offered. We claim that IPNs can be used to decipher how changes in ECM design and connectivity at the local scale affect the fate of cells cultured on biomaterials.

Relationship between corrosion and nanoscale friction on a metallic glass.

Metallic glasses are promising materials for microdevices, although corrosion and friction limit their effectiveness and durability. We investigated nanoscale friction on a metallic glass in corrosive solutions after different periods of immersion time using atomic force microscopy to elucidate the influence of corrosion on nanoscale friction. The evolution of friction upon repeated scanning cycles on the corroded surfaces reveals a bilayer surface oxide film, of which the outer layer is removed by the scanning tip. The measurement of friction and adhesion allows one to compare the physicochemical processes of surface dissolution at the interface of the two layers. The findings contribute to the understanding of mechanical contacts with metallic glasses under corrosive conditions by exploring the interrelation of microscopic corrosion mechanisms and nanoscale friction.

Optoregulated force application to cellular receptors using molecular motors.

Progress in our understanding of mechanotransduction events requires noninvasive methods for the manipulation of forces at molecular scale in physiological environments. Inspired by cellular mechanisms for force application (i.e. motor proteins pulling on cytoskeletal fibers), we present a unique molecular machine that can apply forces at cell-matrix and cell-cell junctions using light as an energy source. The key actuator is a light-driven rotatory molecular motor linked to polymer chains, which is intercalated between a membrane receptor and an engineered biointerface. The light-driven actuation of the molecular motor is converted in mechanical twisting of the entangled polymer chains, which will in turn effectively "pull" on engaged cell membrane receptors (e.g., integrins, T cell receptors) within the illuminated area. Applied forces have physiologically-relevant magnitude and occur at time scales within the relevant ranges for mechanotransduction at cell-friendly exposure conditions, as demonstrated in force-dependent focal adhesion maturation and T cell activation experiments. Our results reveal the potential of nanomotors for the manipulation of living cells at the molecular scale and demonstrate a functionality which at the moment cannot be achieved by other technologies for force application.

Nanomechanics of self-assembled DNA building blocks.

DNA has become a powerful platform to design functional nanodevices. DNA nanodevices are often composed of self-assembled DNA building blocks that differ significantly from the structure of native DNA. In this study, we present Flow Force Microscopy as a massively parallel approach to study the nanomechanics of DNA self-assemblies on the single-molecular level. The high-throughput experiments performed in a simple microfluidic channel enable statistically meaningful studies with nanometer scale precision in a time frame of several minutes. A surprisingly high flexibility was observed for a typical construct used in DNA origami, reflected in a persistence length of 10.2 nm, a factor of five smaller than for native DNA. The enhanced flexibility is attributed to the discontinuous backbone of DNA self-assemblies that facilitate base pair opening by thermal fluctuations at the end of hybridized oligomers. We believe that the results will contribute to the fundamental understanding of DNA nanomechanics and help to improve the design of DNA nanodevices with applications in biological analysis and clinical research.

Tactile perception of randomly rough surfaces.

Most everyday surfaces are randomly rough and self-similar on sufficiently small scales. We investigated the tactile perception of randomly rough surfaces using 3D-printed samples, where the topographic structure and the statistical properties of scale-dependent roughness were varied independently. We found that the tactile perception of similarity between surfaces was dominated by the statistical micro-scale roughness rather than by their topographic resemblance. Participants were able to notice differences in the Hurst roughness exponent of 0.2, or a difference in surface curvature of 0.8 [Formula: see text] for surfaces with curvatures between 1 and 3 [Formula: see text]. In contrast, visual perception of similarity between color-coded images of the surface height was dominated by their topographic resemblance. We conclude that vibration cues from roughness at the length scale of the finger ridge distance distract the participants from including the topography into the judgement of similarity. The interaction between surface asperities and fingertip skin led to higher friction for higher micro-scale roughness. Individual friction data allowed us to construct a psychometric curve which relates similarity decisions to differences in friction. Participants noticed differences in the friction coefficient as small as 0.035 for samples with friction coefficients between 0.34 and 0.45.

Molecular kinetics and cooperative effects in friction and adhesion of fast reversible bonds.

Molecular mechanisms of adhesion and friction include the rupture of single and multiple bonds. The strength of adhesion and friction thus depends on the molecular kinetics and cooperative effects in the lifetime of bonds under stress. We measured the rate dependence of friction and adhesion mediated by supramolecular guest-host bonds using atomic force microscopy (AFM). The tip of the AFM and the surface were functionalized with cyclodextrin hosts. The influence of molecular kinetics on adhesion and friction was studied using three different ditopic guest molecules that connected the AFM tip and the surface. Adamantane, ferrocene, and azobenzene were the guest end groups of the connector molecules that formed inclusion complexes with the cyclodextrin hosts. The results confirm the importance of the molecular off-rate and of cooperative effects for the strength of adhesion and friction. Positive cooperativity also shapes the dependence of friction on the concentration of connector molecules, which follows the Hill-Langmuir model. Based on the Hill coefficient of 3.6, reflecting a characteristic rupture of at least 3-4 parallel bonds, a rescaling of the pulling rate is suggested that shifts the rate dependence of adhesion and friction for the three different molecules towards one master curve.

The mechanics of single cross-links which mediate cell attachment at a hydrogel surface.

The response of cultured cells to the mechanical properties of hydrogel substrates depends ultimately on the response of single crosslinks to external forces exerted at cell attachment points. We prepared hydrogels by co-polymerization of poly(ethylene glycol diacrylate) (PEGDA) and carboxy poly(ethylene glycol) acrylate (ACPEG-COOH) and confirmed fibroblast spreading on the hydrogel after the ACPEG linker was functionalized with the RGD cell adhesive motif. We performed specific force spectroscopy experiments on the same ACPEG linkers in order to probe the mechanics of single cross-links which mediate the cell attachment and spreading. Measurements were performed with tips of an atomic force microscope (AFM) functionalized with streptavidin and ACPEG linkers functionalized with biotin. We compared hydrogels of varying elastic modulus between 4 and 41 kPa which exhibited significant differences in cell spreading. An effective spring constant for the displacement of single cross-links at the hydrogel surface was derived from the distributions of rupture force and molecular stiffness. A factor of ten in the elastic modulus E of the hydrogel corresponded to a factor of five in the effective spring constant k of single crosslinks, indicating a transition in scaling with the mesh size ξ from the macroscopic E∝ξ-3 to the molecular k∝ξ-2. The quantification of stiffness and deformation at the molecular length scale contributes to the discussion of mechanisms in force-regulated phenomena in cell biology.

Friction in Passive Tactile Perception Induces Phase Coherency in Late Somatosensory Single Trial Sequences.

Event related potentials represent a noninvasive means for studying sensory and cognitive processes that occur in response to particular stimuli. Here, we report on a phase measure for estimating single trial interaction of late somatosensory potentials (LSPs) following a tribological well defined mechanical stimulation of the human fingertip. Stimuli are presented via a programmable Braille-display with actively switchable pins which was slid along the apex of the passive fingertip, i.e., the fingertip rested stationarily in a finger holding system with circular opening at the bottom. The event was the raising and the lowering of either one, three, or five lines of pins. Differences were identified by measures based on instantaneous phase synchronization to the stimuli across trials, in particular the wavelet phase synchronization stability (WPSS) measure for single trial sequences of LSPs. In particular, we show that the higher the friction the stronger and more localized the induced phase coherency is. We concluded that the WPSS analysis of single sequences of LSPs represents a reliable method which allows for the quantification of brain responses upon distinct tactile stimuli.

Friction force microscopy of tribochemistry and interfacial ageing for the SiO x /Si/Au system.

Friction force microscopy was performed with oxidized or gold-coated silicon tips sliding on Au(111) or oxidized Si(100) surfaces in ultrahigh vacuum. We measured very low friction forces compared to adhesion forces and found a modulation of lateral forces reflecting the atomic structure of the surfaces. Holding the force-microscopy tip stationary for some time did not lead to an increase in static friction, i.e., no contact ageing was observed for these pairs of tip and surface. Passivating layers from tip or surface were removed in order to allow for contact ageing through the development of chemical bonds in the static contact. After removal of the passivating layers, tribochemical reactions resulted in strong friction forces and tip wear. Friction, wear, and the re-passivation by oxides are discussed based on results for the temporal development of friction forces, on images of the scanned area after friction force microscopy experiments, and on electron microscopy of the tips.

Interactions between shape-persistent macromolecules as probed by AFM.

Water-soluble shape-persistent cyclodextrin (CD) polymers with amino-functionalized end groups were prepared starting from diacetylene-modified cyclodextrin monomers by a combined Glaser coupling/click chemistry approach. Structural perfection of the neutral CD polymers and inclusion complex formation with ditopic and monotopic guest molecules were proven by MALDI-TOF and UV-vis measurements. Small-angle neutron and X-ray (SANS/SAXS) scattering experiments confirm the stiffness of the polymer chains with an apparent contour length of about 130 Å. Surface modification of planar silicon wafers as well as AFM tips was realized by covalent bound formation between the terminal amino groups of the CD polymer and a reactive isothiocyanate-silane monolayer. Atomic force measurements of CD polymer decorated surfaces show enhanced supramolecular interaction energies which can be attributed to multiple inclusion complexes based on the rigidity of the polymer backbone and the regular configuration of the CD moieties. Depending on the geometrical configuration of attachment anisotropic adhesion characteristics of the polymer system can be distinguished between a peeling and a shearing mechanism.

Dynamic shear force microscopy of confined liquids at a gold electrode.

The confinement of liquids in nanometer-scale gaps can lead to changes in their viscous shear properties. For liquids of polar molecules, the charge state of the confining surfaces has a significant influence on the structure in the confined liquid. Here we report on the implementation of dynamic shear force microscopy in an electrochemical cell. Lateral oscillations of the tip of an atomic force microscope were magnetically activated at a frequency of about 50 kHz. The damping of the lateral tip oscillation was recorded as a function of the tip-sample distance and of the electrode potential at the surface of a Au(100) single crystal electrode. The influence of surface charges on the shear response of the nano-confined liquids was demonstrated for the ionic liquid [EMIM][NTf2] and for aqueous Na2SO4 solution.

Single-molecule force spectroscopy of fast reversible bonds.

In single-molecule force spectroscopy, the unbinding force is often used to quantify the interaction strength of single molecular bonds. We analyze force spectroscopy of fast reversible bonds probed in thermodynamic equilibrium by considering the dynamics of force probe and molecular linker. The effect of cantilever and linker dynamics is systematically addressed by measuring the unbinding force of single cyclodextrin inclusion complexes by atomic force spectroscopy for a variety of molecular linkers and varying force probe stiffness. The unbinding force of individual bonds probed in thermodynamic equilibrium is not unique for the molecular system but scales with , the square root of the force probe stiffness, and is largely independent of the molecular linker stiffness. The observations are explained by an effective potential resulting from fast linker fluctuations and fast rebinding kinetics which is probed by an AFM cantilever. The slow cantilever dynamics in the kHz range act as mechanical low pass filter, allowing for fast rebinding kinetics of the molecular complex in the order of 106 kHz. The binding energy of the complex can be estimated from the unbinding force as a function of cantilever stiffness, however with some uncertainty arising from lack of a model in three dimensions.