Measuring Intracellular Viscosity in Conditions of Hypergravity

Woodcock, Emma M.; Girvan, Paul; Eckert, Julia; López‐Duarte, Ismael; Kubánková, Markéta; Loon, Jack J. W. A. van; Brooks, Nicholas J.; Kuimova, Marina K.

doi:10.1016/j.bpj.2019.03.038

Cited by 27 publications

(26 citation statements)

References 56 publications

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“…Increase of F-actin polymerization is associated to an increase in YAP1 activity [57]. The significant up-regulation of YAP1 protein and cytoskeletal adaptations we found, suggest a general stiffening of hypergravity-treated cells, which occurs between 1 and 3 h of treatment, and is coherent with increase of cell motility (see functional tests, Figure 3) but also with other recent LDC results [58] showing increased cell membranes viscosity in osteoblastic and endothelial cells exposed to 15 g.…”

Section: Discussionsupporting

confidence: 89%

Hypergravity Activates a Pro-Angiogenic Homeostatic Response by Human Capillary Endothelial Cells

Cesari

Barravecchia

Pyankova

et al. 2020

IJMS

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Capillary endothelial cells are responsible for homeostatic responses to organismic and environmental stimulations. When malfunctioning, they may cause disease. Exposure to microgravity is known to have negative effects on astronauts’ physiology, the endothelium being a particularly sensitive organ. Microgravity-related dysfunctions are striking similar to the consequences of sedentary life, bed rest, and ageing on Earth. Among different countermeasures implemented to minimize the effects of microgravity, a promising one is artificial gravity. We examined the effects of hypergravity on human microvascular endothelial cells of dermal capillary origin (HMEC-1) treated at 4 g for 15 min, and at 20 g for 15 min, 3 and 6 h. We evaluated cell morphology, gene expression and 2D motility and function. We found a profound rearrangement of the cytoskeleton network, dose-dependent increase of Focal Adhesion kinase (FAK) phosphorylation and Yes-associated protein 1 (YAP1) expression, suggesting cell stiffening and increased proneness to motility. Transcriptome analysis showed expression changes of genes associated with cardiovascular homeostasis, nitric oxide production, angiogenesis, and inflammation. Hypergravity-treated cells also showed significantly improved motility and function (2D migration and tube formation). These results, expanding our knowledge about the homeostatic response of capillary endothelial cells, show that adaptation to hypergravity has opposite effect compared to microgravity on the same cell type.

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Section: Discussionsupporting

confidence: 89%

Hypergravity Activates a Pro-Angiogenic Homeostatic Response by Human Capillary Endothelial Cells

Cesari

Barravecchia

Pyankova

et al. 2020

IJMS

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“…The synthesis of BODIPY 2 was described previously 12 . The new molecular rotor BODIPY 1 was synthesized by modification of the above published procedure 12 , 20 . Full synthetic details and characterization of intermediates and main product can be found in the supplementary information file (SI, Scheme S1 ; Fig.…”

Section: Methodsmentioning

confidence: 99%

Monitoring membrane viscosity in differentiating stem cells using BODIPY-based molecular rotors and FLIM

Kashirina

López‐Duarte

Kubánková

et al. 2020

Sci Rep

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Membrane fluidity plays an important role in many cell functions such as cell adhesion, and migration. In stem cell lines membrane fluidity may play a role in differentiation. Here we report the use of viscosity-sensitive fluorophores based on a BODIPY core, termed "molecular rotors", in combination with Fluorescence Lifetime Imaging Microscopy, for monitoring of plasma membrane viscosity changes in mesenchymal stem cells (MSCs) during osteogenic and chondrogenic differentiation. In order to correlate the viscosity values with membrane lipid composition, the detailed analysis of the corresponding membrane lipid composition of differentiated cells was performed by timeof-flight secondary ion mass spectrometry. Our results directly demonstrate for the first time that differentiation of MSCs results in distinct membrane viscosities, that reflect the change in lipidome of the cells following differentiation. Membrane fluidity is considered a key parameter influencing biological function of cells, such as cell adhesion, migration and differentiation 1. These properties are of particular importance in stem cell lines, where small modifications in membrane parameters have the potential to either promote a lineage commitment or a selfrenewal 2. The plasma membrane is the interface between a cell and its environment, it directly interacts with the matrix outside the cell and is responsible for many important tasks such as signaling and mass transfer. In stem cells, its composition and properties are likely to reflect their differentiation status. However, little is known on how the viscosity parameters of different stem cell lineages can change depending on the direction of differentiation. There is evidence that the membrane fluidity substantially changes during induced pluripotent stem cells (iPS) differentiation. Generalized polarization monitoring was previously used to detect the rise of membrane rigidity during iPSC differentiation 1. Furthermore, the results in 1 potentially suggested that membrane rigidification could be transmitted to neighboring cells, resulting in the acceleration of a cells differentiation, in a wave-line fashion. It was also reported that the viscoelastic properties can predict which subpopulations of undifferentiated mesenchymal stem cells (MSCs) differentiate into osteocytes, and which would turn into adipocytes or chondroblasts. The stiffest cell populations produced more bone cells; the softest cells predominantly produced fat cells; the cells with the highest viscosity became cartilage cells 3. While cell stiffness measured in 3 is a distinctly different property to the cell membrane viscosity, both depend on membrane lipid compositions. There is evidence that differentiation of human mesenchymal stem cells (MSCs) into osteoblasts, chondrocytes or adipocytes produces specific membrane compositions and biophysical properties,

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“…On the other hand, membrane viscosity affects diffusion-controlled reactions [326] and regulates protein movement within the plasma membrane and cytoplasm [327,328], which alters signaling pathways and gene expression. Furthermore, membrane fluidity depends on gravity loading [329][330][331], which most likely affects pharmacodynamics and drug uptake under unnatural gravity conditions [330]. In light of the above findings, both micro-and hyper-gravity may regulate cell membrane biophysical properties and affect cell functioning on a genetic and proteomic level (Figure 5).…”

Section: Gravitational Forces Affecting Biomembranesmentioning

confidence: 96%

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

et al. 2021

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Modifications of the composition or organization of the cancer cell membrane seem to be a promising targeted therapy. This approach can significantly enhance drug uptake or intensify the response of cancer cells to chemotherapeutics. There are several methods enabling lipid bilayer modifications, e.g., pharmacological, physical, and mechanical. It is crucial to keep in mind the significance of drug resistance phenomenon, ion channel and specific receptor impact, and lipid bilayer organization in planning the cell membrane-targeted treatment. In this review, strategies based on cell membrane modulation or reorganization are presented as an alternative tool for future therapeutic protocols.

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Measuring Intracellular Viscosity in Conditions of Hypergravity

Cited by 27 publications

References 56 publications

Hypergravity Activates a Pro-Angiogenic Homeostatic Response by Human Capillary Endothelial Cells

Hypergravity Activates a Pro-Angiogenic Homeostatic Response by Human Capillary Endothelial Cells

Monitoring membrane viscosity in differentiating stem cells using BODIPY-based molecular rotors and FLIM

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

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