Abstract
Stress fibers in the cytoskeleton are essential in maintaining cellular shape and influence cellular adhesion and migration. Cyclic uniaxial stretching results in cellular reorientation orthogonal to the applied stretch direction. The mechanistic cues underlying changes to cellular form and function to stretch stimuli are currently underexplored. We show stretch-induced stress fiber lengthening, their realignment, and increased cortical actin in NIH 3T3 fibroblasts stretched over varied amplitudes and durations. Higher amounts of actin and stress fiber alignment were accompanied with an increase in the effective elastic modulus of cells. Microtubules did not contribute to the measured stiffness or reorientation response but were essential to the nuclear reorientation. We used a phenomenological growth and remodeling law, based on the experimental data, to model stress fiber elongation and reorientation dynamics based on a nonlinear, orthotropic, fiber-reinforced continuum representation of the cell. The model predicts the changes observed fibroblast morphology and increased cellular stiffness under uniaxial cyclic stretch which agrees with experimental results. Such studies are important in exploring the differences underlying mechanotransduction and cellular contractility under stretch.
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Chatterjee A, Kondaiah P, Gundiah N, (2019) Stress fiber growth and remodeling determines cellular morphomechanics under uniaxial cyclic stretch, bioRxiv: https://doi.org/10.1101/622092v1. preprint posted 29 April, 2019
Acknowledgements
We thank Ms. Monisha Mohandas (BSSE, IISc) for help with the AFM. We also thank Ms. Dhulika Ravinuthala who helped in performing some of the uniaxial cyclic stretch experiments reported in this study. NG gratefully acknowledges the Department of Biotechnology (BBI2) and Department of Science and Technology (SERB/003640) for project support. PK laboratory is supported by IISc-DBT partnership program and DST-FIST infrastructure to MRDG.
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AC performed the experiments, analyzed the data, completed the theoretical model, and helped write the manuscript. PK provided inputs on the data interpretation and results. NG designed the study, supervised the research, helped with data analysis, and wrote the manuscript with inputs from all authors.
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Chatterjee, A., Kondaiah, P. & Gundiah, N. Stress fiber growth and remodeling determines cellular morphomechanics under uniaxial cyclic stretch. Biomech Model Mechanobiol 21, 553–567 (2022). https://doi.org/10.1007/s10237-021-01548-z
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DOI: https://doi.org/10.1007/s10237-021-01548-z