Niklas Nordgren

Comparison of different methods to calibrate torsional spring constant and photodetector for atomic force microscopy friction measurements in air and liquid

A number of atomic force microscopy cantilevers have been exhaustively calibrated by a number of techniques to obtain both normal and frictional force constants to evaluate the relative accuracy of the different methods. These were of either direct or indirect character-the latter relies on cantilever resonant frequencies. The so-called Sader [Rev. Sci. Instrum. 70, 3967 (1999)] and Cleveland [Rev. Sci. Instrum. 64, 403 (1993)] techniques are compared for the normal force constant calibration and while agreement was good, a systematic difference was observed. For the torsional force constants, all the techniques displayed a certain scatter but the agreement was highly encouraging. By far the simplest technique is that of Sader, and it is suggested in view of this validation that this method should be generally adopted. The issue of the photodetector calibration is also addressed since this is necessary to obtain the cantilever twist from which the torsional force is calculated. Here a technique of obtaining the torsional photodetector sensitivity by combining the direct and indirect methods is proposed. Direct calibration measurements were conducted in liquid as well as air, and a conversion factor was obtained showing that quantitative friction measurements in liquid are equally feasible provided the correct calibration is performed.

Tunable Nanolubrication between Dual-Responsive Polyionic Grafts

This study reports on a direct approach of quantitatively probing the nanotribological response of chemically end-grafted polyions. A combination of a quartz crystal microbalance with dissipation and atomic force microscopy, in the now well established colloidal probe mode, was utilized to investigate the stimuli-induced lubrication behavior between poly(2-(dimethylamino)ethyl methacrylate) grafts on gold. Force and friction measurements showed reversible transitions of up to an order of magnitude difference induced by varying the solvent conditions. The greatly enhanced lubrication observed at low pH was attributed to the formation of a repulsive, highly charged, hydrated cushion. At high pH the friction was significantly increased. The system turned attractive above the lower critical solution temperature with a small friction reduction interpreted as being due to nanoscopic flattening at the interfacial boundary.

Oncogenes induce a vimentin filament collapse mediated by HDAC6 that is linked to cell stiffness

Significance Oncogenes deregulate fundamental cellular functions, which can lead to the development of tumors and metastases. We show that oncogenes change the spatial organization of the vimentin fibers of the intracellular cytoskeleton, induce cell stiffness, and promote the invasive capacity of cells. We further show that this vimentin reorganization and increased cell stiffness requires histone deacetylase 6 (HDAC6). Taken together, these data support the concept that oncogenes can induce cellular stiffness via HDAC6-dependent reorganization of the vimentin filament network. These findings—that key molecules in oncogenic cell transformation, such as oncogenes and HDAC6, can modulate cell stiffness—highlight the importance of the need for further investigation of the mechanical properties of cells to better understand the mechanisms behind tumor and metastasis formation. Oncogenes deregulate fundamental cellular functions, which can lead to development of tumors, tumor-cell invasion, and metastasis. As the mechanical properties of cells govern cell motility, we hypothesized that oncogenes promote cell invasion by inducing cytoskeletal changes that increase cellular stiffness. We show that the oncogenes simian virus 40 large T antigen, c-Myc, and cyclin E induce spatial reorganization of the vimentin intermediate filament network in cells. At the cellular level, this reorganization manifests as increased width of vimentin fibers and the collapse of the vimentin network. At nanoscale resolution, the organization of vimentin fibers in these oncogene-expressing cells was more entangled, with increased width of the fibers compared with control cells. Expression of these oncogenes also resulted in up-regulation of the tubulin deacetylase histone deacetylase 6 (HDAC6) and altered spatial distribution of acetylated microtubules. This oncogene expression also induced increases in cellular stiffness and promoted the invasive capacity of the cells. Importantly, HDAC6 was required and sufficient for the structural collapse of the vimentin filament network, and was required for increased cellular stiffness of the oncogene-expressing cells. Taken together, these data are consistent with the possibility that oncogenes can induce cellular stiffness via an HDAC6-induced reorganization of the vimentin intermediate filament network.

Top-down grafting of xyloglucan to gold monitored by QCM-D and AFM: enzymatic activity and interactions with cellulose.

This study focuses on the manufacture and characterization of model surfaces consisting of end-grafted xyloglucan (XG), a naturally occurring polysaccharide, onto a gold substrate. The now well-established XET-technology was utilized for enzymatic incorporation of a thiol moiety at one end of the xyloglucan backbone. This functionalized macromolecule was subsequently top-down grafted to gold, forming a thiol-bonded xyloglucan brushlike layer. The grafting was monitored in situ with QCM-D, and a significant difference in the adsorbed/grafted amount between unmodified xyloglucan and the thiol-functionalized polymer was observed. The grafted surface was demonstrated to be accessible to enzyme digestion using the plant endo-xyloglucanase TmNXG1. The nanotribological properties toward cellulose of the untreated crystal, brush-modified surface, and enzyme-exposed surfaces were compared with a view to understanding the role of xyloglucan in friction reduction. Friction coefficients obtained by the AFM colloidal probe technique using a cellulose functionalized probe on the xyloglucan brush showed an increase of a factor of 2 after the enzyme digestion, and this result is interpreted in terms of surface roughness. Finally, the brush is shown to exhibit binding to cellulose despite its highly oriented nature.

Adhesion dynamics for cellulose nanocomposites.

The efficiency of poly(ε-caprolactone) (PCL) as a matrix polymer for cellulose nanocomposites has been investigated at the macromolecular contact level using atomic force microscopy in a colloidal probe configuration. Model cellulose microspheres grafted with PCL were prepared via ring-opening polymerization. Force measurements between the functionalized particles revealed the adhesion to be highly dependent on the contact time because of a diffusion-controlled mechanism. Moreover, an increase of the temperature to 60 degrees C (close to T(m) for the PCL graft) greatly enhanced the adhesion at the polymer-polymer interface, demonstrating the importance of entanglements in the annealing of composite materials.

Mediation of the Nanotribological Properties of Cellulose by Chitosan Adsorption

Cellulosic model surfaces functionalized with chitosan, a naturally occurring cationic biomacromolecule, by in situ adsorption have been studied with an atomic force microscope (AFM) in colloidal probe configuration. The interaction forces on approach and separation, as well as the nanotribological properties, were shown to be highly pH-dependent, and a significant difference in the behavior was seen before and after chitosan adsorption. In general, all forces on approach showed a highly repulsive interaction at shorter distances due to deformation of the probe. At high pH, before chitosan adsorption, a long-range electrostatic repulsion was observed, consistent with DLVO theory. However, at low pH no electrostatic contribution was found before adsorption, probably due to charge neutralization of carboxyl groups. After chitosan adsorption, repulsive forces acting over a much longer distance than predicted by DLVO theory were present at low pH. This effect was ascribed to chain extension of the chitosan species of which the magnitude and the range of the force increased dramatically with higher charge at low pH. In all cases, a typical saw-tooth patterned adhesion was present, with pull-off events occurring at different separations. The frequency of these events after chitosan adsorption was greatly increased at longer distances. Additionally, the adsorbed chitosan markedly reduced the friction, where the largest effect was a 7-fold decrease of the friction coefficient observed at low pH.

Experimental and computational assessment of F-actin influence in regulating cellular stiffness and relaxation behaviour of fibroblasts

In biomechanics, a complete understanding of the structures and mechanisms that regulate cellular stiffness at a molecular level remain elusive. In this paper, we have elucidated the role of filamentous actin (F-actin) in regulating elastic and viscous properties of the cytoplasm and the nucleus. Specifically, we performed colloidal-probe atomic force microscopy (AFM) on BjhTERT fibroblast cells incubated with Latrunculin B (LatB), which results in depolymerisation of F-actin, or DMSO control. We found that the treatment with LatB not only reduced cellular stiffness, but also greatly increased the relaxation rate for the cytoplasm in the peripheral region and in the vicinity of the nucleus. We thus conclude that F-actin is a major determinant in not only providing elastic stiffness to the cell, but also in regulating its viscous behaviour. To further investigate the interdependence of different cytoskeletal networks and cell shape, we provided a computational model in a finite element framework. The computational model is based on a split strain energy function of separate cellular constituents, here assumed to be cytoskeletal components, for which a composite strain energy function was defined. We found a significant influence of cell geometry on the predicted mechanical response. Importantly, the relaxation behaviour of the cell can be characterised by a material model with two time constants that have previously been found to predict mechanical behaviour of actin and intermediate filament networks. By merely tuning two effective stiffness parameters, the model predicts experimental results in cells with a partly depolymerised actin cytoskeleton as well as in untreated control. This indicates that actin and intermediate filament networks are instrumental in providing elastic stiffness in response to applied forces, as well as governing the relaxation behaviour over shorter and longer time-scales, respectively.

Friction Measurement Between Polyester Fibres Using the Fibre Probe SPM

An SPM has been used to measure frictional interactions between two crossed fibres for the first time. The preparation of the surfaces is briefly described, but the crucial element is that the fibr ...

Tablet mechanics depend on nano and micro scale adhesion, lubrication and structure

Tablets are the most convenient form for drug administration. However, despite the ease of manufacturing problems such as powder adhesion occur during the production process. This study presents surface and structural characterization of tablets formulated with commonly used excipients (microcrystalline cellulose (MCC), lactose, mannitol, magnesium (Mg) stearate) pressed under different compaction conditions. Tablet surface analyses were performed with scanning electron microscopy (SEM), profilometry and atomic force microscopy (AFM). The mechanical properties of the tablets were evaluated with a tablet hardness test. Local adhesion detected by AFM decreased when Mg stearate was present in the formulation. Moreover, the tablet strength of plastically deformable excipients such as MCC was significantly decreased after addition of Mg stearate. Combined these facts indicate that Mg stearate affects the particle-particle bonding and thus elastic recovery. The MCC excipient also displayed the highest hardness which is characteristic for a highly cohesive material. This is discussed in the view of the relatively high adhesion found between MCC and a hydrophilic probe at the nanoscale using AFM. In contrast, the tablet strength of brittle materials like lactose and mannitol is unaffected by Mg stearate. Thus fracture occurs within the excipient particles and not at particle boundaries, creating new surfaces not previously exposed to Mg stearate. Such uncoated surfaces may well promote adhesive interactions with tools during manufacture.

Nanomechanical properties of human skin and introduction of a novel hair indenter.

The mechanical resistance of the stratum corneum, the outermost layer of skin, to deformation has been evaluated at different length scales using Atomic Force Microscopy. Nanomechanical surface mapping was first conducted using a sharp silicon tip and revealed that Young׳s modulus of the stratum corneum varied over the surface with a mean value of about 0.4GPa. Force indentation measurements showed permanent deformation of the skin surface only at high applied loads (above 4µN). The latter effect was further demonstrated using nanomechanical imaging in which the obtained depth profiles clearly illustrate the effects of increased normal force on the elastic/plastic surface deformation. Force measurements utilizing the single hair fiber probe supported the nanoindentation results of the stratum corneum being highly elastic at the nanoscale, but revealed that the lateral scale of the deformation determines the effective elastic modulus.This result resolves the fact that the reported values in the literature vary greatly and will help to understand the biophysics of the interaction of razor cut hairs that curl back during growth and interact with the skin.