A Bio-chemo-mechanical Model for Cell Contractility, Adhesion, Signaling, and Stress-Fiber Remodeling
A bio-chemo-mechanical model is described that targets contractility, adhesion, signaling, and cytoskeleton formation and remodeling, where the effort in the case of the last phenomena is focused on actomyosin stress-fibers. The contractility of the cell
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Abstract A bio-chemo-mechanical model is described that targets contractility, adhesion, signaling, and cytoskeleton formation and remodeling, where the effort in the case of the last phenomena is focused on actomyosin stress-fibers. The contractility of the cell is driven by the stress-fibers, which also determine much of the active and passive mechanics that characterize the cell’s mechanical behavior. The stress-fibers attach to adhesion proteins that connect the cell to an extracellular matrix or to a substrate, and apply contractile force through them. This in turn generates signals that can trigger cytoskeleton formation and remodeling. The signals can also arise from external sources such as nervous impulses and biochemical changes to the cell’s surroundings. The model is installed as a user element in a finite element code and used to simulate cell behavior in vitro, such as contraction on a compliant, smooth, flat substrate, or on a bed of compliant posts. Interactions with patterned substrates are also modeled, such as where cells have a limited area to which they can adhere, or where the cells interact with grooves. The results of these simulations are very encouraging as they are largely consistent with observed cell behavior.
1 Introduction About 10 years ago we became interested in the biomechanics of eukaryotic cells, mainly due to the experiments of Chen and coworkers (Tan et al. 2003), where cells are placed on a bed of small compliant posts and, adhering to them, contract and cause bending of the posts. The post deflections can be measured, and as a result the forces being applied by the cell, typically on the scale of tens of nanonewtons, can R.M. McMeeking (B) University of California, Santa Barbara, CA, USA e-mail: [email protected] R.M. McMeeking University of Aberdeen, Aberdeen, UK V.S. Deshpande University of Cambridge, Cambridge, UK © Springer International Publishing Switzerland 2017 G.A. Holzapfel and R.W. Ogden (eds.), Biomechanics: Trends in Modeling and Simulation, Studies in Mechanobiology, Tissue Engineering and Biomaterials 20, DOI 10.1007/978-3-319-41475-1_2
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R.M. McMeeking and V.S. Deshpande
be quantified. Many interesting phenomena emerge from such experiments, such as how cells interact with posts of various levels of stiffness, and with differing numbers of posts. These phenomena are paralleled by equivalent observations of cells on compliant, smooth, flat substrates, or on patterned substrates consisting of topography (say grooves) or limited segments to which the cell can adhere. We developed a bio-chemo-mechanical model for the cell contractility, its adhesion to its substrate whether smooth or post-like, the relevant biochemical signaling that goes on inside the cell, and the consequent activity within the cell such as cytoskeleton formation and remodeling. Our purpose in developing the model was to aid in the development of a deeper understanding of the cell behavior being observed in the experiments, and to support the development of further experimenta
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