000261633 001__ 261633
000261633 005__ 20190619220059.0
000261633 022__ $$a0044-2267
000261633 022__ $$a1521-4001
000261633 02470 $$2isi$$a000450004800002
000261633 0247_ $$a10.1002/zamm.201700368$$2doi
000261633 037__ $$aARTICLE
000261633 245__ $$aA model for cellular mechanotransduction and contractility at finite strain
000261633 260__ $$c2018
000261633 269__ $$a2018
000261633 336__ $$aReviews
000261633 520__ $$aIn this work we introduce a theoretical and computational modeling framework for the contractile response of single cells triggered by external mechanical stimuli. The structural response due to the formation and dissociation of stress fibers is modeled following isotropic anisotropic contractile phases with an orientation that evolves with time and strain. The passive and active structural components are postulated to act in parallel, and the re-orientation process drives the anisotropic phase of stress fiber orientation to align with the direction of the maximum principal stretch. A reduced form of the Hai-Murphy model is used to follow kinetics of myosin states considering the combined effect of "latch"- and "cross"-bridge states. The introduction of distinct isotropic and anisotropic activation allows modeling of the contractile intensity of each phase. Tractions on the cell surface initiate bio-chemical signaling through the RhoA pathway, which in turn controls both myosin contraction and F-actin polymerization. A signaling model is introduced to effectively connect intracellular events with the tractions on the cell surface. The overall model is defined by a free energy density function that couples the deformation and the activation, and associated equilibrium and kinetic models for evolution. Features of the model are highlighted via implementation in a finite element model and application to benchmark problems. The model captures the dynamic contractile responses of cells and stress fiber re-alignment under complex load histories. For example, physiologically relevant scenario such as relaxation of cells to their initial state upon removal of applied loads can be simulated.
000261633 650__ $$aMathematics, Applied
000261633 650__ $$aMechanics
000261633 650__ $$aMathematics
000261633 650__ $$aMechanics
000261633 6531_ $$acell contractility
000261633 6531_ $$aintracellular signaling
000261633 6531_ $$amechanotransduction
000261633 6531_ $$astress fibers
000261633 6531_ $$asmooth-muscle contraction
000261633 6531_ $$amechanical model
000261633 6531_ $$aforce generation
000261633 6531_ $$acollagen gels
000261633 6531_ $$acells
000261633 6531_ $$aphosphorylation
000261633 6531_ $$amechanobiology
000261633 6531_ $$areorientation
000261633 6531_ $$acytoskeleton
000261633 6531_ $$atraction
000261633 700__ $$g277273$$aBouklas, N.$$0250519
000261633 700__ $$g265227$$aSakar, Selman$$0249720
000261633 700__ $$0246474$$aCurtin, W. A.$$g211624
000261633 773__ $$q1754-1770$$k10$$j98$$tZamm-Zeitschrift Fur Angewandte Mathematik Und Mechanik
000261633 8560_ $$fselman.sakar@epfl.ch
000261633 909C0 $$zMarselli, Béatrice$$xU12614$$pLAMMM$$myi.hu@epfl.ch$$0252513
000261633 909C0 $$zMarselli, Béatrice$$xU13117$$pMICROBS$$mselman.sakar@epfl.ch$$0252582
000261633 909CO $$preview$$particle$$ooai:infoscience.epfl.ch:261633$$pSTI
000261633 961__ $$amanon.velasco@epfl.ch
000261633 973__ $$sPUBLISHED$$aEPFL$$rREVIEWED
000261633 980__ $$aARTICLE
000261633 981__ $$aoverwrite