title: Formation of contractile networks and fibers in the medial cell cortex through myosin-II turnover, contraction, and stress-stabilization.
abstract: The morphology of adhered cells depends crucially on the formation of a contractile meshwork of parallel and cross-linked fibers along the contacting surface. The motor activity and minifilament assembly of non-muscle myosin-II is an important component of cortical cytoskeletal remodeling during mechanosensing. We used experiments and computational modeling to study cortical myosin-II dynamics in adhered cells. Confocal microscopy was used to image the medial cell cortex of HeLa cells stably expressing myosin regulatory light chain tagged with GFP (MRLC-GFP). The distribution of MRLC-GFP fibers and focal adhesions was classified into three types of network morphologies. Time-lapse movies show: myosin foci appearance and disappearance; aligning and contraction; stabilization upon alignment. Addition of blebbistatin, which perturbs myosin motor activity, leads to a reorganization of the cortical networks and to a reduction of contractile motions. We quantified the kinetics of contraction, disassembly and reassembly of myosin networks using spatio-temporal image correlation spectroscopy (STICS). Coarse-grained numerical simulations include bipolar minifilaments that contract and align through specified interactions as basic elements. After assuming that minifilament turnover decreases with increasing contractile stress, the simulations reproduce stress-dependent fiber formation in between focal adhesions above a threshold myosin concentration. The STICS correlation function in simulations matches the function measured in experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness.
authors: Department of Physics, Lehigh University, Bethlehem, Pennsylvania.
authors: Wei
authors: W
authors: Nie
authors: Ming-Tzo
authors: MT
authors: Wei
authors: H Daniel
authors: HD
authors: Ou-Yang
authors: Sabrina S
authors: SS
authors: Jedlicka
authors: Dimitrios
authors: D
authors: Vavylonis
mesh_terms: D006801:Humans; D008962:Models, Theoretical; D009119:Muscle Contraction; D024462:Myosin Type II / Q000378:metabolism*; D010766:Phosphorylation; D022502:Stress Fibers
chemical_list: D024462:Myosin Type II
keywords: cell cortex; image correlation spectroscopy; mathematical modeling; myosin; stress fibers
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