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1.
Nat Commun ; 15(1): 3000, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38589403

ABSTRACT

Actomyosin networks constrict cell area and junctions to alter cell and tissue shape. However, during cell expansion under mechanical stress, actomyosin networks are strengthened and polarized to relax stress. Thus, cells face a conflicting situation between the enhanced actomyosin contractile properties and the expansion behaviour of the cell or tissue. To address this paradoxical situation, we study late Drosophila oogenesis and reveal an unusual epithelial expansion wave behaviour. Mechanistically, Rac1 and Rho1 integrate basal pulsatile actomyosin networks with ruffles and focal adhesions to increase and then stabilize basal area of epithelial cells allowing their flattening and elongation. This epithelial expansion behaviour bridges cell changes to oocyte growth and extension, while oocyte growth in turn deforms the epithelium to drive cell spreading. Basal pulsatile actomyosin networks exhibit non-contractile mechanics, non-linear structures and F-actin/Myosin-II spatiotemporal signal separation, implicating unreported expanding properties. Biophysical modelling incorporating these expanding properties well simulates epithelial cell expansion waves. Our work thus highlights actomyosin expanding properties as a key mechanism driving tissue morphogenesis.


Subject(s)
Actomyosin , Drosophila Proteins , Animals , Actomyosin/metabolism , Drosophila Proteins/metabolism , Epithelial Cells/metabolism , Actin Cytoskeleton/metabolism , Drosophila/metabolism , Epithelium/metabolism , Morphogenesis
2.
Nat Commun ; 15(1): 1471, 2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38368368

ABSTRACT

How paracrine signals are interpreted to yield multiple cell fate decisions in a dynamic context during human development in vivo and in vitro remains poorly understood. Here we report an automated tracking method to follow signaling histories linked to cell fate in large numbers of human pluripotent stem cells (hPSCs). Using an unbiased statistical approach, we discover that measured BMP signaling history correlates strongly with fate in individual cells. We find that BMP response in hPSCs varies more strongly in the duration of signaling than the level. However, both the level and duration of signaling activity control cell fate choices only by changing the time integral. Therefore, signaling duration and level are interchangeable in this context. In a stem cell model for patterning of the human embryo, we show that signaling histories predict the fate pattern and that the integral model correctly predicts changes in cell fate domains when signaling is perturbed. Our data suggest that mechanistically, BMP signaling is integrated by SOX2.


Subject(s)
Pluripotent Stem Cells , Humans , Cell Differentiation , Signal Transduction
3.
Nat Methods ; 20(12): 1859-1862, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38057513
4.
Acta Biomater ; 141: 178-189, 2022 03 15.
Article in English | MEDLINE | ID: mdl-35041902

ABSTRACT

Hydrogels are widely used as substrates to investigate interactions between cells and their microenvironment as they mimic many attributes of the extracellular matrix. The stiffness of hydrogels is an important property that is known to regulate cell behavior. Beside stiffness, cells also respond to structural cues such as mesh size. However, since the mesh size of hydrogel is intrinsically coupled to its stiffness, its role in regulating cell behavior has never been independently investigated. Here, we report a hydrogel system whose mesh size and stiffness can be independently controlled. Cell behavior, including spreading, migration, and formation of focal adhesions is significantly altered on hydrogels with different mesh sizes but with the same stiffness. At the transcriptional level, hydrogel mesh size affects cellular mechanotransduction by regulating nuclear translocation of yes-associated protein. These findings demonstrate that the mesh size of a hydrogel plays an important role in cell-substrate interactions. STATEMENT OF SIGNIFICANCE: Hydrogels are ideal platforms with which to investigate interactions between cells and their microenvironment as they mimic many physical properties of the extracellular matrix. However, the mesh size of hydrogels is intrinsically coupled to their stiffness, making it challenging to investigate the contribution of mesh size to cell behavior. In this work, we use hydrogel-on-glass substrates with defined thicknesses whose stiffness and mesh size can be independently tuned. We use these substrates to isolate the effects of mesh size on cell behavior, including attachment, spreading, migration, focal adhesion formation and YAP localization in the nucleus. Our results show that mesh size has significant, yet often overlooked, effects, on cell behavior, and contribute to a further understanding of cell-substrate interactions.


Subject(s)
Hydrogels , Mechanotransduction, Cellular , Extracellular Matrix/metabolism , Focal Adhesions , Hydrogels/chemistry , Surgical Mesh
5.
Phys Rev E ; 102(1-1): 012405, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32794908

ABSTRACT

Cell division is central for embryonic development, tissue morphogenesis, and tumor growth. Experiments have evidenced that mitotic cell division is manipulated by the intercellular cues such as cell-cell junctions. However, it still remains unclear how these cortical-associated cues mechanically affect the mitotic spindle machinery, which determines the position and orientation of the cell division. In this paper, a mesoscopic dynamic cell division model is established to explore the integrated regulations of cortical polarity, microtubule pulling forces, cell deformability, and internal osmotic pressure. We show that the distributed pulling forces of astral microtubules play a key role in encoding the instructive cortical cues to orient and position the spindle of a dividing cell. The present model can not only predict the spindle orientation and position, but also capture the morphological evolution of cell rounding. The theoretical results agree well with relevant experiments both qualitatively and quantitatively. This work sheds light on the mechanical linkage between cell cortex and mitotic spindle, and holds potential in regulating cell division and sculpting tissue morphology.


Subject(s)
Cell Division , Epithelial Cells/cytology , Models, Biological , Biomechanical Phenomena , Mitosis , Osmotic Pressure , Spindle Apparatus/metabolism
6.
Biophys J ; 112(11): 2377-2386, 2017 Jun 06.
Article in English | MEDLINE | ID: mdl-28591610

ABSTRACT

Cell spreading is involved in many physiological and pathological processes. The spreading behavior of a cell significantly depends on its microenvironment, but the biochemomechanical mechanisms of geometry-confined cell spreading remain unclear. A dynamic model is here established to investigate the spreading of cells confined in a finite region with different geometries, e.g., rectangle, ellipse, triangle, and L-shape. This model incorporates both biophysical and biochemical mechanisms, including actin polymerization, integrin-mediated binding, plasma viscoelasticity, and the elasticity of membranes and microtubules. We simulate the dynamic configurational evolution of a cell under different geometric microenvironments, including the angular distribution of microtubule forces and the deformation of the nucleus. The results indicate that the positioning of the cell-division plane is affected by its boundary confinement: a cell divides in a plane perpendicular to its minimal principal axis of inertia of area. In addition, the effects of such physical factors as the adhesive bond density, membrane tension, and microtubule number are examined on the cell spreading dynamics. The theoretical predictions show a good agreement with relevant experimental results. This work sheds light on the geometry-confined spreading dynamics of cells and holds potential applications in regulating cell division and designing cell-based sensors.


Subject(s)
Cell Enlargement , Models, Biological , Actins/metabolism , Animals , Cell Division/physiology , Cell Nucleus/physiology , Computer Simulation , Elasticity , Integrins/metabolism , Microtubules/metabolism , Surface Tension , Viscosity
7.
Sci Rep ; 6: 28907, 2016 07 19.
Article in English | MEDLINE | ID: mdl-27432079

ABSTRACT

Cattail or Typha, an emergent aquatic macrophyte widely distributed in lakes and other shallow water areas, has slender blades with a chiral morphology. The wind-resilient Typha blades can produce distinct hydraulic resistance for ecosystem functions. However, their stem may rupture and dislodge in excessive wind drag. In this paper, we combine fluid dynamics simulations and experimental measurements to investigate the aeroelastic behavior of Typha blades in wind. It is found that the chirality-dependent flutter, including wind-induced rotation and torsion, is a crucial strategy for Typha blades to accommodate wind forces. Flow visualization demonstrates that the twisting morphology of blades provides advantages over the flat one in the context of two integrated functions: improving wind resistance and mitigating vortex-induced vibration. The unusual dynamic responses and superior mechanical properties of Typha blades are closely related to their biological/ecosystem functions and macro/micro structures. This work decodes the physical mechanisms of chirality-dependent flutter in Typha blades and holds potential applications in vortex-induced vibration suppression and the design of, e.g., bioinspired flight vehicles.

8.
Int J Clin Exp Med ; 8(8): 12609-16, 2015.
Article in English | MEDLINE | ID: mdl-26550172

ABSTRACT

Long non-coding RNAs (lncRNAs) UCA1 have been shown to paly an important regulatory roles in cancer biology, and UCA1 dysfunction is related to TNM stage, metastasis and postoperative survival in several cancers. However, the biological role and clinical significance of UCA1 in the carcinogenesis of prostate cancer (PC) remain largely unclear. Herein, we found that UCA1 was abnormally upregulated in tumor tissues from PC patients, and patients with high UCA1 levels had a significantly poorer prognosis. Intriguingly, the mRNA and protein levels of KLF4 were significantly increased in tumor tissues, which was highly correlated to UCA1 levels. Moreover, UCA1 depletion inhibited the growth and induced apoptosis in PC3 and LNCaP cell lines. In addition, UCA1 loss-of-function could decrease KLF4 expression, subsequently, the downregulation of KRT6 and KRT13. Taken together, our study indicated that UCA1 had a crucial role in the tumorigenesis of PC. Moreover, UCA1 loss-of-function inhibited cell proliferation and induced cell apoptosis, at least partially, through inactivation KLF4-KRT6/13 cascade.

9.
Ying Yong Sheng Tai Xue Bao ; 26(10): 3103-10, 2015 Oct.
Article in Chinese | MEDLINE | ID: mdl-26995919

ABSTRACT

Considering the characteristics of rice production and climate conditions in Southwest China, an agricultural drought monitoring model based on wetness index anomaly rate (Mp) by calculating the variation of deviation from average values of relative humid index was established, and was used to analyze the spatial-temporal distribution characteristics of the rice drought during the growth season in Southwest China in the past 50 years (1961-2010). The applicability of the Mp model in Southwest China was verified by using this model to monitor the rice drought. The result showed there was a decreasing trend in the frequency of rice drought in term of the decadal variability. The areas with high drought risk mainly concentrated in northwestern and mid-eastern Yunnan Province, eastern Sichuan Basin, northeastern Chongqing City, and southeastern Guizhou Province. The drought frequency was highest at the stage from transplanting to tasseling, followed by the stage from grain filling to maturity, and was lowest at the stage from tasseling to grain filling. Mp was suitable for monitoring the rice drought in Southwest China, and could be used as a reference for the rice planting areas without irrigation data.


Subject(s)
Agriculture , Droughts , Oryza/growth & development , China , Climate Change , Ecosystem , Models, Theoretical , Spatio-Temporal Analysis
10.
Opt Lett ; 35(11): 1758, 2010 Jun 01.
Article in English | MEDLINE | ID: mdl-20517406

ABSTRACT

We show that research presented in Opt. Lett.34, 301 (2009)OPLEDP0146-959210.1364/OL.34.000301 applied questionable phosphor definitions and a questionable simulation procedure for light-emitting diodes. Our simulation indicates that a one-dimensional photonic crystal is beneficial for color control but cannot improve the light extraction as asserted in that Letter.

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