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Stress relaxation microscopy: Imaging local stress in cells
Authors:Susana Moreno-Flores  Rafael Benitez  Maria dM Vivanco  José Luis Toca-Herrera
Institution:1. Biosurfaces unit, CIC BiomaGUNE, Paseo Miramón 182, 20009 San Sebastián-Donostia, Spain;2. Department of Mathematics, Centro Universitario de Plasencia, Universidad de Extremadura, Avda. Virgen del Puerto 2, 10600 Plasencia, Spain;3. Cell Biology & Stem Cells Unit, CIC BioGUNE, Parque tecnológico de Bizkaia, Ed. 801A, 48160 Derio, Spain;1. Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA;2. Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA;3. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA;4. Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH 44195, USA;5. Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA;6. Department of Oncology, London Health Science Center, Schulich School of Medicine & Dentistry, Western University, London, Ontario N6A 4L6, Canada;1. State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing, PR China;2. Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University, Beijing, PR China;3. Department of Mechanical Engineering, University of Alberta, Edmonton, AB, Canada;1. Biophysics Group, Department of Physics, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany;2. Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany;3. IB3: Institute of Biological Chemistry, Biophysics and Bioengineering, Department of Physics, Heriot-Watt University, Edinburgh, United Kingdom
Abstract:Biomechanics is gaining relevance as complementary discipline to structural and cellular biology. The response of cells to mechanical stimuli determines cell type and function, while the spatial distribution of mechanical forces within the cells is crucial to understand cell activity. The experimental methodologies to approach cell mechanics are diverse but either they are effective in few cases or they rule out the innate cell complexity. In this regard, we have developed a simple scanning probe-based methodology that overcomes the limitations of the available methods. Stress relaxation, the decay of the force exerted by the cell surface at constant deformation, has been used to extract relaxational responses at each cellular sublocalisation and generate maps. Surprisingly, decay curves exerted by test cells are fully described by a generalized viscoelastic model that accounts for more than one simultaneously occurring relaxations. Within the range of applied forces (0.5–4 nN) a slow and a fast relaxation with characteristic times of 0.1 and 1 s have been detected and assigned to rearrangements of cell membrane and cytoskeleton, respectively. Relaxation time mapping of entire cells is thus promising to simultaneously detect non-uniformities in membrane and cytoskeleton and as identifying tool for cell type and disease.
Keywords:
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