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A biomechanical perspective on stress fiber structure and function.

ABSTRACT: Stress fibers are actomyosin-based bundles whose structural and contractile properties underlie numerous cellular processes including adhesion, motility and mechanosensing. Recent advances in high-resolution live-cell imaging and single-cell force measurement have dramatically sharpened our understanding of the assembly, connectivity, and evolution of various specialized stress fiber subpopulations. This in turn has motivated interest in understanding how individual stress fibers generate tension and support cellular structure and force generation. In this review, we discuss approaches for measuring the mechanical properties of single stress fibers. We begin by discussing studies conducted in cell-free settings, including strategies based on isolation of intact stress fibers and reconstitution of stress fiber-like structures from purified components. We then discuss measurements obtained in living cells based both on inference of stress fiber properties from whole-cell mechanical measurements (e.g., atomic force microscopy) and on direct interrogation of single stress fibers (e.g., subcellular laser nanosurgery). We conclude by reviewing various mathematical models of stress fiber function that have been developed based on these experimental measurements. An important future challenge in this area will be the integration of these sophisticated biophysical measurements with the field's increasingly detailed molecular understanding of stress fiber assembly, dynamics, and signal transduction. This article is part of a Special Issue entitled: Mechanobiology.

SUBMITTER: Kassianidou E

PROVIDER: S-EPMC4589434 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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A biomechanical perspective on stress fiber structure and function.

Kassianidou Elena E Kumar Sanjay S

Biochimica et biophysica acta 20150417 11 Pt B

Stress fibers are actomyosin-based bundles whose structural and contractile properties underlie numerous cellular processes including adhesion, motility and mechanosensing. Recent advances in high-resolution live-cell imaging and single-cell force measurement have dramatically sharpened our understanding of the assembly, connectivity, and evolution of various specialized stress fiber subpopulations. This in turn has motivated interest in understanding how individual stress fibers generate tensio ...[more]

PMID: 25896524

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Project description:Fluid shear stress differentially regulates endothelial cell stress fiber formation with decreased stress fibers in areas of disturbed flow compared with steady flow areas. Importantly, stress fibers are critical for several endothelial cell functions including cell shape, mechano-signal transduction, and endothelial cell-cell junction integrity. A key mediator of steady flow-induced stress fiber formation is Src that regulates downstream signaling mediators such as phosphorylation of cortactin, activity of focal adhesion kinase, and small GTPases.Previously, we showed that thioredoxin-interacting protein (TXNIP, also VDUP1 [vitamin D upregulated protein 1] and TBP-2 [thioredoxin binding protein 2]) was regulated by fluid shear stress; TXNIP expression was increased in disturbed flow compared with steady flow areas. Although TXNIP was originally characterized for its role in redox and metabolic cellular functions, recent reports show important scaffold functions related to its ?-arrestin structure. Based on these findings, we hypothesized that TXNIP acts as a biomechanical sensor that regulates Src kinase activity and stress fiber formation.Using en face immunohistochemistry of the aorta and cultured endothelial cells, we show inverse relationship between TXNIP expression and Src activity. Specifically, steady flow increased Src activity and stress fiber formation, whereas it decreased TXNIP expression. In contrast, disturbed flow had opposite effects. We studied the role of TXNIP in regulating Src homology phosphatase-2 plasma membrane localization and vascular endothelial cadherin binding because Src homology phosphatase-2 indirectly regulates dephosphorylation of Src tyrosine 527 that inhibits Src activity. Using immunohistochemistry and immunoprecipitation, we found that TXNIP prevented Src homology phosphatase-2-vascular endothelial cadherin interaction.In summary, these data characterize a fluid shear stress-mediated mechanism for stress fiber formation that involves a TXNIP-dependent vascular endothelial cadherin-Src homology phosphatase-2-Src pathway.

Project description:The collagen fiber architecture of the peripapillary sclera (PPS), which surrounds the scleral canal, is a critical factor in determining the mechanical response of the optic nerve head (ONH) to variations in intraocular pressure (IOP). Experimental and clinical evidence point to IOP-induced deformations within the scleral canal as important contributing factors of glaucomatous neural tissue damage and consequent vision loss. Hence, it is imperative to understand PPS architecture and biomechanics. Current consensus is that the fibers of the PPS form a closed ring around the canal to support the delicate neural tissues within. We propose an alternative fiber architecture for the PPS, in which the scleral canal is supported primarily by long-running fibers oriented tangentially to the canal. We present evidence that this tangential model is consistent with histological observations in multiple species, and with quantitative measurements of fiber orientation obtained from small angle light scattering and wide-angle X-ray scattering. Using finite element models, we investigated the biomechanical implications of a tangential fiber PPS architecture. We found that the tangential arrangement of fibers afforded better mechanical support to the tissues within the scleral canal as compared to a simple circumferential ring of fibers or a combination of fibers oriented radially and circumferentially. We also found that subtle variations from a tangential orientation could reproduce clinically observed ONH behavior which has yet to be explained using current theories of PPS architecture and simulation, namely, the contraction of the scleral canal under elevated IOP.Statement of significanceIt is hypothesized that vision loss in glaucoma is due to excessive mechanical deformation within the neural tissue inside the scleral canal. This study proposes a new model for how the collagen of the peripapillary sclera surrounding the canal is organized to support the delicate neural tissue inside. Previous low-resolution studies of the peripapillary sclera suggested that the collagen fibers are arranged in a ring around the canal. Instead, we provide microscopic evidence suggesting that the canal is also supported by long-running interwoven fibers oriented tangentially to the canal. We demonstrate that this arrangement has multiple biomechanical advantages over a circular collagen arrangement and can explain previously unexplained experimental findings including contraction of the scleral canal under elevated intraocular pressure.

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A biomechanical perspective on stress fiber structure and function.

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A biomechanical perspective on stress fiber structure and function.

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