Chapter 19 Mechanical Response of Cytoskeletal Networks

Department of Physics and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA.
Methods in cell biology (Impact Factor: 1.42). 02/2008; 89:487-519. DOI: 10.1016/S0091-679X(08)00619-5
Source: PubMed

ABSTRACT The cellular cytoskeleton is a dynamic network of filamentous proteins, consisting of filamentous actin (F-actin), microtubules, and intermediate filaments. However, these networks are not simple linear, elastic solids; they can exhibit highly nonlinear elasticity and a thermal dynamics driven by ATP-dependent processes. To build quantitative mechanical models describing complex cellular behaviors, it is necessary to understand the underlying physical principles that regulate force transmission and dynamics within these networks. In this chapter, we review our current understanding of the physics of networks of cytoskeletal proteins formed in vitro. We introduce rheology, the technique used to measure mechanical response. We discuss our current understanding of the mechanical response of F-actin networks, and how the biophysical properties of F-actin and actin cross-linking proteins can dramatically impact the network mechanical response. We discuss how incorporating dynamic and rigid microtubules into F-actin networks can affect the contours of growing microtubules and composite network rigidity. Finally, we discuss the mechanical behaviors of intermediate filaments.

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Available from: Margaret L Gardel, Aug 15, 2014
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    • "The molecular nature of the contribution of tubulin to cell nanomechanics has been investigated in detail (Gardel et al. 2008). So far, the microtubule network is supposed to represent a compressive load-bearing component that counteracts the tensile forces generated by the cortical actimyosin web (Ingber 2003). "
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    ABSTRACT: The mechanical characteristics of endothelial cells reveal four distinct compartments, namely glycocalyx, cell cortex, cytoplasm and nucleus. There is accumulating evidence that endothelial nanomechanics of these individual compartments control vascular physiology. Depending on protein composition, filament formation and interaction with cross-linker proteins, these four compartments determine endothelial stiffness. Structural organization and mechanical properties directly influence physiological processes such as endothelial barrier function, nitric oxide release and gene expression. This review will focus on endothelial nanomechanics and its impact on vascular function.
    Cell and Tissue Research 03/2014; 355(3). DOI:10.1007/s00441-014-1853-5 · 3.57 Impact Factor
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    • "Cytoskeleton is required for many biological processes, such as embryonic morphogenesis, immune surveillance, tissue repair, and regeneration. Aberrant regulation of cytoskeleton dynamics drives progression of cancer invasion and metastasis [1, 2]. Cancer cell metastasis is a multistage process involving invasion into surrounding tissue, intravasation, transit in the blood or lymph, extravasation, and growth at a new site. "
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    ABSTRACT: The objective of this study was performed to investigate the effects of thapsigargin on apoptosis, actin cytoskeletal dynamics, and actin cytoskeletal proteins in human lung adenocarcinoma cell. Thapsigargin is a specific irreversible inhibitor of ER calcium-ATPase, which may promote ER stress by depletion of lumenal calcium stores and show potential to induce cell death. The effects of thapsigargin on the apoptosis in A549 cells were assayed by Hoechst staining. Moreover, the F-actin staining by Rhodamine-phalloidin and RhoA antibody for cytoskeleton organizations were applied to A549 cells. To confirm the impairment of cytoskeletal dynamics treated with thapsigargin, western blots were applied to analyze the protein levels of p-Cofilin-1 (Ser3), Cofilin-1, and pPaxillin (Tyr118), as well as RhoA and pS6 (S240/244). Results suggest that thapsigargin may induce cell death in A549 cells with a time- and dose-dependent manner. The F-actin fibers and RhoA signals are also reduced with a time- and dose-dependent manner by thapsigargin treatment. The phosphorylation forms of Cofilin-1 and paxillin are attenuated by 1 μ M thapsigargin treatment for 24 h. These alternations may be caused by the inhibition of of mTORC1 activities (indicated by pS6 (Ser240/244)) and RhoA pathways after thapsigargin treatment. The present findings highlight important roles of calcium entry in cytoskeleton organization and apoptosis in human lung adenocarcinoma cells and will help to set a stage to the clinical treatment of cancer cell metastasis.
    The Scientific World Journal 01/2014; 2014(2):619050. DOI:10.1155/2014/619050 · 1.73 Impact Factor
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    • "First, it is proposed to be an important component of sensing mechanisms, which translate the mechanical cues into biochemical signals [3], [4]. Second, the cytoskeleton is a stress-bearing structure that maintains cellular integrity and morphology and it serves as an actuator through adaption of its architecture [5], [6]. Due to these important properties, particular emphasis in cellular biomechanics has been given to the acto-myosin system [2], [7]. "
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    ABSTRACT: Mechanical forces can regulate various functions in living cells. The cytoskeleton is a crucial element for the transduction of forces in cell-internal signals and subsequent biological responses. Accordingly, many studies in cellular biomechanics have been focused on the role of the contractile acto-myosin system in such processes. A widely used method to observe the dynamic actin network in living cells is the transgenic expression of fluorescent proteins fused to actin. However, adverse effects of GFP-actin fusion proteins on cell spreading, migration and cell adhesion strength have been reported. These shortcomings were shown to be partly overcome by fusions of actin binding peptides to fluorescent proteins. Nevertheless, it is not understood whether direct labeling by actin fusion proteins or indirect labeling via these chimaeras alters biomechanical responses of cells and the cytoskeleton to forces. We investigated the dynamic reorganization of actin stress fibers in cells under cyclic mechanical loading by transiently expressing either egfp-Lifeact or eyfp-actin in rat embryonic fibroblasts and observing them by means of live cell microscopy. Our results demonstrate that mechanically-induced actin stress fiber reorganization exhibits very different kinetics in EYFP-actin cells and EGFP-Lifeact cells, the latter showing a remarkable agreement with the reorganization kinetics of non-transfected cells under the same experimental conditions.
    PLoS ONE 08/2011; 6(8):e22941. DOI:10.1371/journal.pone.0022941 · 3.23 Impact Factor
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