Sarcomere Mechanics in Capillary Endothelial Cells

Russell, Robert John; Xia, Shen‐Ling; Dickinson, Richard B.; Lele, Tanmay P.

doi:10.1016/j.bpj.2009.07.017

Cited by 49 publications

(66 citation statements)

References 35 publications

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“…Additionally, this large-scale mechanosensitive regulation by the contractility of actin-myosin fibers could also explain the linear relationship that we obtained between the saturation force and stiffness (Fig. 2C): The constant deformation of around 840 nm could be attributed to the simultaneous shortening of several micron-sized sarcomeric substructures within actomyosin stress fibers that, according to previous studies (44,45), can sustain contractions of 10-25%.…”

Section: Dynamics Of Focal Adhesions and Traction Force Measurements Onsupporting

confidence: 78%

Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness

Trichet

Digabel

Hawkins

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

513

521

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Cell migration plays a major role in many fundamental biological processes, such as morphogenesis, tumor metastasis, and wound healing. As they anchor and pull on their surroundings, adhering cells actively probe the stiffness of their environment. Current understanding is that traction forces exerted by cells arise mainly at mechanotransduction sites, called focal adhesions, whose size seems to be correlated to the force exerted by cells on their underlying substrate, at least during their initial stages. In fact, our data show by direct measurements that the buildup of traction forces is faster for larger substrate stiffness, and that the stress measured at adhesion sites depends on substrate rigidity. Our results, backed by a phenomenological model based on active gel theory, suggest that rigidity-sensing is mediated by a large-scale mechanism originating in the cytoskeleton instead of a local one. We show that large-scale mechanosensing leads to an adaptative response of cell migration to stiffness gradients. In response to a step boundary in rigidity, we observe not only that cells migrate preferentially toward stiffer substrates, but also that this response is optimal in a narrow range of rigidities. Taken together, these findings lead to unique insights into the regulation of cell response to external mechanical cues and provide evidence for a cytoskeleton-based rigidity-sensing mechanism.actin cytoskeleton | microfabrication | mechanobiology | cell mechanics C ell migration is not only sensitive to the biochemical composition of the environment, but also to its mechanical properties. Cells directly probe the physical properties of their environment, such as substrate stiffness, by pulling on it. Increasing evidence show that matrix or tissue elasticity has a key role in regulating numerous cell functions, such as adhesion (1), migration (2) and differentiation (3). Such functions are affected by cell-generated actomyosin forces that depend on substrate stiffness through a feedback mechanism (4). The sensitivity of cells to mechanical properties of the extracellular matrix (ECM) arises from the mechanosensitive nature of cell adhesion. Numerous plausible candidates for the transduction of mechanochemical signals have been tested (5). Among them, focal adhesions (FAs) appear to be the most prominent, as shown by the reported correlation between their area and sustained force exhibiting a constant stress (6-9). This mechanosensitivity is usually accounted for by a generic local mechanism in which a force applied to an FA induces an elastic deformation of the contact that triggers conformational and organizational changes of some of its constitutive proteins, which in turn can enhance binding with new proteins enabling growth of the contact (10-12). However, how this local mechanosensitivity can result in the ability of cells to sense and respond to the rigidity of their surroundings (2, 3, 13, 14) at a large scale remains largely unknown (5, 15). Much conflicting evidence has emerged from a variety of studi...

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Section: Dynamics Of Focal Adhesions and Traction Force Measurements Onsupporting

confidence: 78%

Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness

Trichet

Digabel

Hawkins

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

513

521

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“…Previous studies have produced several models that suggest that retraction length scales with SF length but make no predictions on how SF contractility and stiffness vary with SF length (14)(15)(16). Our results show that the relationship between SF length and dissipated elastic energy after SLA is more complex than previously appreciated and offers insights into this intricate relationship.…”

Section: Discussionmentioning

confidence: 57%

Geometry and network connectivity govern the mechanics of stress fibers

Kassianidou

Brand

Schwarz

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Actomyosin stress fibers (SFs) play key roles in driving polarized motility and generating traction forces, yet little is known about how tension borne by an individual SF is governed by SF geometry and its connectivity to other cytoskeletal elements. We now address this question by combining single-cell micropatterning with subcellular laser ablation to probe the mechanics of single, geometrically defined SFs. The retraction length of geometrically isolated SFs after cutting depends strongly on SF length, demonstrating that longer SFs dissipate more energy upon incision. Furthermore, when cell geometry and adhesive spacing are fixed, cell-to-cell heterogeneities in SF dissipated elastic energy can be predicted from varying degrees of physical integration with the surrounding network. We apply genetic, pharmacological, and computational approaches to demonstrate a causal and quantitative relationship between SF connectivity and mechanics for patterned cells and show that similar relationships hold for nonpatterned cells allowed to form cell-cell contacts in monolayer culture. Remarkably, dissipation of a single SF within a monolayer induces cytoskeletal rearrangements in cells long distances away. Finally, stimulation of cell migration leads to characteristic changes in network connectivity that promote SF bundling at the cell rear. Our findings demonstrate that SFs influence and are influenced by the networks in which they reside. Such higher order network interactions contribute in unexpected ways to cell mechanics and motility.cytoskeleton | active cable model | actin | myosin | cell migration

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“…Since then, a number of different methods, ranging from explicit measurements (Sugita et al, 2011) to observations of direct consequences -e.g. deformations of the underlying substrate (Balaban et al, 2001;Trichet et al, 2012), or stress fiber retraction following laser cutting (Colombelli et al, 2009;Kumar et al, 2006;Russell et al, 2009) -have established that stress fibers are, in fact, constantly under tension. Therefore, whereas muscles can rapidly switch from rest to full power stroke, stress fibers remain at a quasiconstant operational level.…”

Section: Stress Fiber Diversity and Interdependence With Focal Adhesionsmentioning

confidence: 99%

The inner workings of stress fibers − from contractile machinery to focal adhesions and back

Livne

Geiger

2016

Journal of Cell Science

167

153

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Ventral stress fibers and focal adhesions are physically coupled structures that play key roles in cellular mechanics and force sensing. The tight functional interdependence between the two is manifested not only by their apparent proximity but also by the fact that ventral stress fibers and focal adhesions are simultaneously diminished upon actomyosin relaxation, and grow when subjected to external stretching. However, whereas the apparent co-regulation of the two structures is well-documented, the underlying mechanisms remains poorly understood. In this Commentary, we discuss some of the fundamental, yet still open questions regarding ventral stress fiber structure, its force-dependent assembly, as well as its capacity to generate force. We also challenge the common approach -i.e. ventral stress fibers are variants of the well-studied striated or smooth muscle machinery -by presenting and critically discussing alternative venues. By highlighting some of the less-explored aspects of the interplay between stress fibers and focal adhesions, we hope that this Commentary will encourage further investigation in this field.

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Sarcomere Mechanics in Capillary Endothelial Cells

Cited by 49 publications

References 35 publications

Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness

Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness

Geometry and network connectivity govern the mechanics of stress fibers

The inner workings of stress fibers − from contractile machinery to focal adhesions and back

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