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  • 1.
    Florea, Cristina
    et al.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Tanska, Petri
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Mononen, Mika
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center of Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Laasanen, Mikko
    School of Engineering and Technology, Savonia University of Applied Sciences, Kuopio, Finland.
    Korhonen, Rami
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland.
    A combined experimental atomic force microscopy-based nanoindentation and computational modeling approach to unravel the key contributors to the time-dependent mechanical behavior of single cells2017In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 16, no 1, p. 297-311, article id 27554263Article in journal (Refereed)
    Abstract [en]

    Cellular responses to mechanical stimuli are influenced by the mechanical properties of cells and the surrounding tissue matrix. Cells exhibit viscoelastic behavior in response to an applied stress. This has been attributed to fluid flow-dependent and flow-independent mechanisms. However, the particular mechanism that controls the local time-dependent behavior of cells is unknown. Here, a combined approach of experimental AFM nanoindentation with computational modeling is proposed, taking into account complex material behavior. Three constitutive models (porohyperelastic, viscohyperelastic, poroviscohyperelastic) in tandem with optimization algorithms were employed to capture the experimental stress relaxation data of chondrocytes at 5 % strain. The poroviscohyperelastic models with and without fluid flow allowed through the cell membrane provided excellent description of the experimental time-dependent cell responses (normalized mean squared error (NMSE) of 0.003 between the model and experiments). The viscohyperelastic model without fluid could not follow the entire experimental data that well (NMSE = 0.005), while the porohyperelastic model could not capture it at all (NMSE = 0.383). We also show by parametric analysis that the fluid flow has a small, but essential effect on the loading phase and short-term cell relaxation response, while the solid viscoelasticity controls the longer-term responses. We suggest that the local time-dependent cell mechanical response is determined by the combined effects of intrinsic viscoelasticity of the cytoskeleton and fluid flow redistribution in the cells, although the contribution of fluid flow is smaller when using a nanosized probe and moderate indentation rate. The present approach provides new insights into viscoelastic responses of chondrocytes, important for further understanding cell mechanobiological mechanisms in health and disease.

  • 2.
    Turunen, Siru
    et al.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Saarakkala, Simo
    Department of Diagnostic Radiology, University of Oulu, Oulu, Finland; Oulu University Hospital, Oulu, Finland.
    Han, Sang-Kuy
    Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Canada; Mechanical and Manufacturing Engineering, Schulich School of Engineering, University of Calgary, Calgary, Canada; Fischell Department of Bioengineering, Clark School of Engineering, University of Maryland, Maryland, USA.
    Herzog, Walter
    Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Canada; Mechanical and Manufacturing Engineering, Schulich School of Engineering, University of Calgary, Calgary, Canada.
    Tanska, Petri
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Korhonen, Rami
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    The effect of collagen degradation on chondrocyte volume and morphology in bovine articular cartilage following a hypotonic challenge2013In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 12, no 3, p. 417-429Article in journal (Refereed)
    Abstract [en]

    Collagen degradation is one of the early signs of osteoarthritis. It is not known how collagen degradation affects chondrocyte volume and morphology. Thus, the aim of this study was to investigate the effect of enzymatically induced collagen degradation on cell volume and shape changes in articular cartilage after a hypotonic challenge. Confocal laser scanning microscopy was used for imaging superficial zone chondrocytes in intact and degraded cartilage exposed to a hypotonic challenge. Fourier transform infrared microspectroscopy, polarized light microscopy, and mechanical testing were used to quantify differences in proteoglycan and collagen content, collagen orientation, and biomechanical properties, respectively, between the intact and degraded cartilage. Collagen content decreased and collagen orientation angle increased significantly (p < 0.05) in the superficial zone cartilage after collagenase treatment, and the instantaneous modulus of the samples was reduced significantly (p < 0.05). Normalized cell volume and height 20 min after the osmotic challenge (with respect to the original volume and height) were significantly (p < 0.001 and p < 0.01, respectively) larger in the intact compared to the degraded cartilage. These findings suggest that the mechanical environment of chondrocytes, specifically collagen content and orientation, affects cell volume and shape changes in the superficial zone articular cartilage when exposed to osmotic loading. This emphasizes the role of collagen in modulating cartilage mechanobiology in diseased tissue.

  • 3. Turunen, Siru
    et al.
    Lammi, Mikko
    Department of Biosciences, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Saarakkala, Simo
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Department of Diagnostic Radiology, University of Oulu and Oulu University Hospital, Oulu, Finland .
    Koistinen, Arto
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; BioMater Centre, University of Eastern Finland, Kuopio, Finland.
    Korhonen, Rami
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland .
    Hypotonic challenge modulates cell volumes differently in the superficial zone of intact articular cartilage and cartilage explant.2012In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 11, no 5, p. 665-75, article id 21877192Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to evaluate the effect of sample preparation on the biomechanical behaviour of chondrocytes. We compared the volumetric and dimensional changes of chondrocytes in the superficial zone (SZ) of intact articular cartilage and cartilage explant before and after a hypotonic challenge. Calcein-AM labelled SZ chondrocytes were imaged with confocal laser scanning microscopy through intact cartilage surfaces and through cut surfaces of cartilage explants. In order to clarify the effect of tissue composition on cell volume changes, Fourier Transform Infrared microspectroscopy was used for estimating the proteoglycan and collagen contents of the samples. In the isotonic medium (300 mOsm), there was a significant difference (p < 0.05) in the SZ cell volumes and aspect ratios between intact cartilage samples and cartilage explants. Changes in cell volumes at both short-term (2 min) and long-term (2 h) time points after the hypotonic challenge (180 mOsm) were significantly different (p < 0.05) between the groups. Further, proteoglycan content was found to correlate significantly (r(2) = 0.63, p < 0.05) with the cell volume changes in cartilage samples with intact surfaces. Collagen content did not correlate with cell volume changes. The results suggest that the biomechanical behaviour of chondrocytes following osmotic challenge is different in intact cartilage and in cartilage explant. This indicates that the mechanobiological responses of cartilage and cell signalling may be significantly dependent on the integrity of the mechanical environment of chondrocytes.

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