Oscillatory Microrheology, Creep Compliance and Stress Relaxation of Biological Cells Reveal Strong Correlations as Probed by Atomic Force Microscopy

The mechanical properties of cells are important for many biological processes, including wound healing, cancers, and embryogenesis. Currently, our understanding of cell mechanical properties remains incomplete. Different techniques have been used to probe different aspects of the mechanical properties of cells, among them microplate rheology, optical tweezers, micropipette aspiration, and magnetic twisting cytometry. These techniques have given rise to different theoretical descriptions, reaching from simple Kelvin-Voigt or Maxwell models to fractional such as power law models, and their combinations. Atomic force microscopy (AFM) is a flexible technique that enables global and local probing of adherent cells. Here, using an AFM, we indented single retinal pigmented epithelium cells adhering to the bottom of a culture dish. The indentation was performed at two locations: above the nucleus, and towards the periphery of the cell. We applied creep compliance, stress relaxation, and oscillatory rheological tests to wild type and drug modified cells. Considering known fractional and semi-fractional descriptions, we found the extracted parameters to correlate. Moreover, the Young’s modulus as obtained from the initial indentation strongly correlated with all of the parameters from the applied power-law descriptions. Our study shows that the results from different rheological tests are directly comparable. This can be used in the future, for example, to reduce the number of measurements in planned experiments. Apparently, under these experimental conditions, the cells possess a limited number of degrees of freedom as their rheological properties change

Recording Lifetime Behavior and Movement in an Invertebrate Model

Characterization of lifetime behavioral changes is essential for understanding aging and aging-related diseases. However, such studies are scarce partly due to the lack of efficient tools. Here we describe and provide proof of concept for a stereo vision system that classifies and sequentially records at an extremely fine scale six different behaviors (resting, micro-movement, walking, flying, feeding and drinking) and the within-cage (3D) location of individual tephritid fruit flies by time-of-day throughout their lives. Using flies fed on two different diets, full sugar-yeast and sugar-only diets, we report for the first time their behavioral changes throughout their lives at a high resolution. We have found that the daily activity peaks at the age of 15–20 days and then gradually declines with age for flies on both diets. However, the overall daily activity is higher for flies on sugar-only diet than those on the full diet. Flies on sugar-only diet show a stronger diurnal localization pattern with higher preference to staying on the top of the cage during the period of light-off when compared to flies on the full diet. Clustering analyses of age-specific behavior patterns reveal three distinct young, middle-aged and old clusters for flies on each of the two diets. The middle-aged groups for flies on sugar-only diet consist of much younger age groups when compared to flies on full diet. This technology provides research opportunities for using a behavioral informatics approach for understanding different ways in which behavior, movement, and aging in model organisms are mutually affecting

Cytosolic actin isoforms form networks with different rheological properties that indicate specific biological function

Abstract The implications of the existence of different actins expressed in epithelial cells for network mechanics and dynamics is investigated by microrheology and confocal imaging. γ-actin predominately found in the apical cortex forms stiffer networks compared to β-actin, which is preferentially organized in stress fibers. We attribute this to selective interactions with Mg2+-ions interconnecting the filaments’ N-termini. Bundling propensity of the isoforms is different in the presence of Mg2+-ions, while crosslinkers such as α-actinin, fascin, and heavy meromyosin alter the mechanical response independent of the isoform. In the presence of myosin, β-actin networks show a large number of small contraction foci, while γ-actin displays larger but fewer foci indicative of a stronger interaction with myosin motors. We infer that subtle changes in the amino acid sequence of actin isoforms lead to alterations of the mechanical properties on the network level with potential implications for specific biological functions

The Dutch Measure for quantification of Treatment Resistance in Depression (DM-TRD): an extension of the Maudsley Staging Method.

Item does not contain fulltextBackground: Treatment resistant depression (TRD) is common in daily practice. An empirical, widely accepted and applicable measure to quantify TRD is lacking. Previously, the Maudsley Staging Method (MSM) showed good validity. We aimed to improve the MSM by refining and extending its items resulting in the Dutch Measure for quantification of TRD (DM-TRD). Methods: In addition to duration, severity and failed treatments in the current depressive episode, we added items for functional impairment, comorbid anxiety, personality disorders and psychosocial stressors. We extended the augmentation section and added items for failed psychotherapy and intensified treatment. We examined psychometric properties of the DM-TRD and tested prediction of future depressive symptoms and remission after 16 weeks in 274 (DSM-IV) depressed in- and outpatients entering naturalistic treatment. Results: The DM-TRD showed excellent inter-/intra-rater reliability. Higher scores were associated with more symptoms and less remission during follow-up. The DM-TRD outperformed the MSM in prediction of future depressive symptomatology. Remission was predicted equally well by both measures. Longer duration of the current episode, larger functional impairment and larger baseline symptom severity were the strongest predictors of symptomatology at follow-up. Longer duration and larger functional impairment were negatively associated with remission. Limitations: Longer follow-up could have increased predictive power. Addition of items for somatic co-morbidity, childhood adversity and psychotic features must be investigated further. Conclusion: The DM-TRD has excellent psychometric properties and better predictive validity for clinical outcome than other sophisticated measure published to date. Its use in clinical practice and research will improve treatment planning in TRD-patients.7 p

New perspectives in studying active faults in metropolitan France: the 'Active faults France' (FACT/ATS) research axis from the Resif-Epos consortium

Mainland France is part of a plate interior with a strong structural heritage, undergoing a low rate of deformation, where destructive earthquakes can nevertheless occur. In this paper, we emphasize that the knowledge of active faults is still largely fragmentary, and that significant efforts are needed to generate robust data, in particular on the numerous faults, that still lack any study. This is the aim of the 'Failles ACTives France' (FACT) axis launched in the framework of the Transverse Seismicity Action (ATS) of the Resif-Epos consortium. We present some recent investigations carried out along suspected active faults in mountainous areas, their forelands and remote lowlands, which implement new approaches and new tools, and allow characterizing their Quaternary activity