Adherent cells use forces at the cell-substrate interface to sense and respond to the physical properties of their environment. These cell forces can be measured with traction force microscopy which ...inverts the equations of elasticity theory to calculate them from the deformations of soft polymer substrates. We introduce a new type of traction force microscopy that in contrast to traditional methods uses additional image data for cytoskeleton and adhesion structures and a biophysical model to improve the robustness of the inverse procedure and abolishes the need for regularization. We use this method to demonstrate that ventral stress fibers of U2OS-cells are typically under higher mechanical tension than dorsal stress fibers or transverse arcs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cytoskeletal mechanics regulates cell morphodynamics and many physiological processes. While contractility is known to be largely RhoA-dependent, the process by which localized biochemical signals ...are translated into cell-level responses is poorly understood. Here we combine optogenetic control of RhoA, live-cell imaging and traction force microscopy to investigate the dynamics of actomyosin-based force generation. Local activation of RhoA not only stimulates local recruitment of actin and myosin but also increased traction forces that rapidly propagate across the cell via stress fibres and drive increased actin flow. Surprisingly, this flow reverses direction when local RhoA activation stops. We identify zyxin as a regulator of stress fibre mechanics, as stress fibres are fluid-like without flow reversal in its absence. Using a physical model, we demonstrate that stress fibres behave elastic-like, even at timescales exceeding turnover of constituent proteins. Such molecular control of actin mechanics likely plays critical roles in regulating morphodynamic events.
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.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Surface contraction waves (SCWs) in oocytes and embryos lead to large-scale shape changes coupled to cell cycle transitions and are spatially coordinated with the cell axis. Here, we show that SCWs ...in the starfish oocyte are generated by a traveling band of myosin II-driven cortical contractility. At the front of the band, contractility is activated by removal of cdk1 inhibition of the RhoA/RhoA kinase/myosin II signaling module, while at the rear, contractility is switched off by negative feedback originating downstream of RhoA kinase. The SCW's directionality and speed are controlled by a spatiotemporal gradient of cdk1-cyclinB. This gradient is formed by the release of cdk1-cyclinB from the asymmetrically located nucleus, and progressive degradation of cyclinB. By combining quantitative imaging, biochemical and mechanical perturbations with mathematical modeling, we demonstrate that the SCWs result from the spatiotemporal integration of two conserved regulatory modules, cdk1-cyclinB for cell cycle regulation and RhoA/Rok/NMYII for actomyosin contractility.Surface contraction waves (SCWs) are prominent shape changes coupled to cell cycle transitions in oocytes. Here the authors show that SCWs are patterned by the spatiotemporal integration of two conserved modules, cdk1-cyclinB for cell cycle regulation and RhoA/Rok/NMYII for actomyosin contractility.
The shape of animal cells is an important regulator for many essential processes such as cell migration or division. It is strongly determined by the organization of the actin cytoskeleton, which is ...also the main regulator of cell forces. Quantitative analysis of cell shape helps to reveal the physical processes underlying cell shape and forces, but it is notoriously difficult to conduct it in three dimensions. Here we use direct laser writing to create 3D open scaffolds for adhesion of connective tissue cells through well-defined adhesion platforms. Due to actomyosin contractility in the cell contour, characteristic invaginations lined by actin bundles form between adjacent adhesion sites. Using quantitative image processing and mathematical modeling, we demonstrate that the resulting shapes are determined not only by contractility, but also by elastic stress in the peripheral actin bundles. In this way, cells can generate higher forces than through contractility alone.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A Supplementary Information file from a different paper was inadvertently published with the original version of this Article. This file was replaced with the correct Supplementary Information file ...on 24 October 2017.
The creation of local and global maps is crucial for (semi-)autonomous operation of mobile robots in previously unknown environments, e.g. during search and rescue missions. We developed an on-board ...stereo-vision based mapping system, thereby introducing local obstacle maps that can directly be used for fast local obstacle avoidance and path planning. In addition, we designed them to constitute a suitable input to a widely-used simultaneous localization and mapping (SLAM) algorithm. We performed experiments in unknown indoor, unstructured outdoor as well as mixed environments and demonstrated the applicability of our method to camera setups with small as well as wide field of view. In all three scenarios, we achieved a final 2D position error of less than 0.08% of the full trajectory.
Actinic keratosis (AK) affects millions of people worldwide, and its prevalence continues to increase. AK lesions are caused by chronic ultraviolet radiation exposure, and the presence of two or more ...AK lesions along with photodamage should raise the consideration of a diagnosis of field cancerization. Effective treatment of individual lesions as well as field cancerization is essential for good long-term outcomes. The Swiss Registry of Actinic Keratosis Treatment (REAKT) Working Group has developed clinical practice guidelines for the treatment of field cancerization in patients who present with AK. These guidelines are intended to serve as a resource for physicians as to the most appropriate treatment and management of AK and field cancerization based on current evidence and the combined practical experience of the authors. Treatment of AK and field cancerization should be driven by consideration of relevant patient, disease, and treatment factors, and appropriate treatment decisions will differ from patient to patient. Prevention measures and screening recommendations are discussed, and special considerations related to management of immunocompromised patients are provided.
Joint simultaneous localization and mapping (SLAM) constitutes the basis for cooperative action in multi‐robot teams. We designed a stereo vision‐based 6D SLAM system combining local and global ...methods to benefit from their particular advantages: (1) Decoupled local reference filters on each robot for real‐time, long‐term stable state estimation required for stabilization, control and fast obstacle avoidance; (2) Online graph optimization with a novel graph topology and intra‐ as well as inter‐robot loop closures through an improved submap matching method to provide global multi‐robot pose and map estimates; (3) Distribution of the processing of high‐frequency and high‐bandwidth measurements enabling the exchange of aggregated and thus compacted map data. As a result, we gain robustness with respect to communication losses between robots. We evaluated our improved map matcher on simulated and real‐world datasets and present our full system in five real‐world multi‐robot experiments in areas of up 3,000 m2 (bounding box), including visual robot detections and submap matches as loop‐closure constraints. Further, we demonstrate its application to autonomous multi‐robot exploration in a challenging rough‐terrain environment at a Moon‐analogue site located on a volcano.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although the precise underlying pathomechanisms of psoriasis have not been fully elucidated, previous reports suggest that T helper 1-type cytokines are critically involved in the pathogenesis of ...this disease. Interleukin-12 (IL-12), a heterodimeric cytokine, has been suggested to play a major role in the development of T helper 1 cell responses. In this study, the presence of IL-12 mRNA and protein was investigated in normal human skin as well as nonlesional and lesional psoriatic skin. Messenger RNA levels were determined in biopsy specimens by a standard and a nested reverse transcriptase-polymerase chain reaction method. Additionally, IL-12 protein expression was analyzedin situ by immunohistochemistry using an antibody recognizing IL-12 p70. Whereas specific transcripts for IL-12 p35 were reproducibly detected without any significant differences in all samples, enhanced IL-12 p40 mRNA signals were only found in lesional psoriatic skin as compared with normal and nonlesional psoriatic skin. Furthermore, immunoreactivity for IL-12 p70 was markedly increased in the psoriatic skin lesions and was predominantly expressed on mononuclear cells in the dermis. In conclusion, our data suggest a critical role for IL-12 in promoting and maintaining T cell activation and inducing T helper 1-type cytokines such as interferon-γ in psoriasis. We speculate that IL-12 might be a key cytokine in the pathogenesis of psoriasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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