Micropatterning as a tool to identify regulatory triggers and kinetics of actin-mediated endothelial mechanosensing

Gegenfurtner, Florian; Jahn, Bérénice; Wagner, H.; Ziegenhain, Christoph; Enard, Wolfgang; Rädler, Joachim O.; Vollmar, Angelika M.; Zahler, Stefan

doi:10.1242/jcs.212886

Cited by 25 publications

(19 citation statements)

References 65 publications

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“…The confocal images illustrate that confinement leads to dramatic changes in cell shape, in addition to changes in mechanics and YAP localization. Importantly, cellular elongation has been reported to alter cytoarchitecture and YAP localization independent of topographical confinement ( Bao et al , 2017 ; Gegenfurtner et al , 2018 ). This raises the possibility that narrow channels might induce softening and YAP localization by altering cell shape rather than by introducing mechanical constrictions ( Bao et al , 2017 ; Gegenfurtner et al , 2018 ).…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, cellular elongation has been reported to alter cytoarchitecture and YAP localization independent of topographical confinement ( Bao et al , 2017 ; Gegenfurtner et al , 2018 ). This raises the possibility that narrow channels might induce softening and YAP localization by altering cell shape rather than by introducing mechanical constrictions ( Bao et al , 2017 ; Gegenfurtner et al , 2018 ). To experimentally separate elongation and mechanical confinement, we conducted a parallel set of studies in which we cultured cells on fibronectin (FN) 1D microlines of widths ranging from 2 to 100 µm (Supplemental Figures S6 and S7).…”

Section: Resultsmentioning

confidence: 99%

“…These results are consistent with previous work in which YAP nuclear localization closely tracks actomyosin assembly and contractility ( Elosegui-Artola et al , 2017 ) and confirm the role of YAP in mechanotransduction ( Dupont et al , 2011 ; Raghunathan et al , 2014 ; Nardone et al , 2017 ). Previous studies observed that cellular elongation has a role in altering cytoarchitecture and YAP localization independently of topographical confinement ( Bao et al , 2017 ; Gegenfurtner et al , 2018 ). Notably, YAP remained in the nucleus for cells on 1D microlines, indicating that cell softening and YAP function intrinsically depends on topographical confinement and is not simply being driven by changes in cellular elongation.…”

Section: Discussionmentioning

confidence: 98%

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Direct evidence that tumor cells soften when navigating confined spaces

Rianna

Radmacher

Kumar

2020

MBoC

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

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Direct evidence that tumor cells soften when navigating confined spaces

Rianna

Radmacher

Kumar

2020

MBoC

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“…Cells sense the mechanical properties of their surroundings and receive mechanical stimuli from neighboring cells and from the extracellular matrix (ECM) [8][9][10][11]. Cell migration follows elasticity gradients [12][13][14][15], and cancer spreading [16] and metastases formation [17] as well as many other cellular processes, such as neuron growth or vascular tube formation by endothelial cells, can be stimulated and guided by ECM elasticity [18][19][20][21]. In order to design and construct functional tissue substitutes, knowledge and control of the elastic parameters of these hydrogels are therefore essential, and methods to characterize the mechanical properties of tissue-engineered structures with high spatial resolution are a prerequisite for this task.…”

Section: Introductionmentioning

confidence: 99%

Contactless Vibrational Analysis of Transparent Hydrogel Structures Using Laser-Doppler Vibrometry

et al. 2020

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Background Investigating the mechanical properties of biological and biocompatible hydrogels is important in tissue engineering and biofabrication. Atomic force microscopy (AFM) and compression testing are routinely used to determine mechanical properties of tissue and tissue constructs. However, these techniques are slow and require mechanical contact with the sample, rendering in situ measurements difficult. Objective We therefore aim at a fast and contactless method for determining the mechanical properties of biological hydrogels and investigate if an optical method, like Laser-Doppler vibrometry (LDV), can accomplish this task. Methods LDV is a fast contactless method for mechanical analysis. Nonetheless, LDV setups operating in the visible range of the optical spectrum are difficult to use for transparent materials, such as biological hydrogels, because LDV relies on reflected or back-scattered light from the sample. We therefore use a near-infrared (NIR) scanning LDV to determine the vibration spectra of cylindrical gelatin discs of different gelatin concentration and compare the results to AFM data and unconfined compression testing. Results We show that the gelatin test structures can be analyzed, using a NIR LDV, and the Young’s moduli can be deduced from the resonance frequencies of the first normal (0,1) mode of these structures. As expected, the frequency of this mode increases with the square root of the Young’s modulus and the damping constant increases exponentially with gelatin concentration, which underpins the validity of our approach. Conclusions Our results demonstrate that NIR wavelengths are suitable for a fast, contactless vibrational analysis of transparent hydrogel structures.

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“…However, novel approaches to measure cell‐generated forces and material properties have emerged that can begin to fill this gap. [ 132,139–142 ]…”

Section: Measuring Cell and Tissue Mechanical Properties For Mechanotmentioning

confidence: 99%

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Pradhan

Banda

Farino

et al. 2020

Adv Healthcare Materials

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The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.

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Micropatterning as a tool to identify regulatory triggers and kinetics of actin-mediated endothelial mechanosensing

Cited by 25 publications

References 65 publications

Direct evidence that tumor cells soften when navigating confined spaces

Direct evidence that tumor cells soften when navigating confined spaces

Contactless Vibrational Analysis of Transparent Hydrogel Structures Using Laser-Doppler Vibrometry

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

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