The Actin Cortex: A Bridge between Cell Shape and Function

The cortical actin network controls many animal cell shape changes by locally modulating cortical tension. Recent work has provided insight into cortex components and regulators. However, how the network is reorganized in response to cellular signaling, and the role reorganization may play during cell state changes, remain to be determined

Nuclear mechanotransduction in stem cells.

In development and in homeostatic maintenance of tissues, stem cells and progenitor cells are constantly subjected to forces. These forces can lead to significant changes in gene expression and function of stem cells, mediating self-renewal, lineage specification, and even loss of function. One of the ways that has been proposed to mediate these functional changes in stem cells is nuclear mechanotransduction - the process by which forces are converted to signals in the nucleus. The purpose of this review is to discuss the means by which mechanical signals are transduced into the nucleus, through the linker of nucleoskeleton and cytoskeleton (LINC) complex and other nuclear envelope transmembrane (NET) proteins, which connect the cytoskeleton to the nucleus. We discuss how LINC/NETs confers tissue-specific mechanosensitivity to cells and further elucidate how LINC/NETs acts as a control center for nuclear mechanical signals, regulating both gene expression and chromatin organization. Throughout, we primarily focus on stem cell-specific examples, notwithstanding that this is a nascent field. We conclude by highlighting open questions and pointing the way to enhanced research efforts to understand the role nuclear mechanotransduction plays in cell fate choice

The Characterization of the Magdalene in the Gospels according to John, Thomas, Philip and Mary

The recent interest in the figure of Mary Magdalene in pop culture has seemingly generated a fascination in studying the Magdalene academically. As a figure who is negatively and often wrongly characterized as a sinner, a prostitute and sexual partner to Jesus, the Magdalene is also a significant literary character who symbolizes the power of the feminine and the feminine right to salvation. Using both diachronic and synchronic methodologies we can begin to understand the power and influence of the Magdalene in both the canonical gospels and other Christian texts at Nag Hammadi. The character of the Magdalene is examined in the Gospels according to John, Thomas, Philip and Mary where her character advances the plot and aids the reader in understanding the theological message of each gospel. Within these selected texts, the relationship that the Magdalene has with Jesus and the competition that exists between Mary and Peter is emphasized. The texts are examined using a gender-critical approach to illustrate the role that gender and sex play in the development, as well as in the reception of the text. Using a combination of diachronic, synchronic as well as a gender-critical approach we are able to understand how the Magdalene highlights the unity in Christ and gives empowerment to female literary characters

Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate

Cell fate transitions are frequently accompanied by changes in cell shape and mechanics. However, how cellular mechanics affects the instructive signaling pathways controlling cell fate is poorly understood. To probe the interplay between shape, mechanics, and fate, we use mouse embryonic stem cells (ESCs), which change shape as they undergo early differentiation. We find that shape change is regulated by a b-cateninmediated decrease in RhoA activity and subsequent decrease in the plasma membrane tension. Strikingly, preventing a decrease in membrane tension results in early differentiation defects in ESCs and gastruloids. Decreased membrane tension facilitates the endocytosis of FGF signaling components, which activate ERK signaling and direct the exit from the ESC state. Increasing Rab5a-facilitated endocytosis rescues defective early differentiation. Thus, we show that a mechanically triggered increase in endocytosis regulates early differentiation. Our findings are of fundamental importance for understanding how cell mechanics regulates biochemical signaling and therefore cell fate

Three-dimensional geometry controls division symmetry in stem cell colonies.

Proper control of division orientation and symmetry, largely determined by spindle positioning, is essential to development and homeostasis. Spindle positioning has been extensively studied in cells dividing in two-dimensional (2D) environments and in epithelial tissues, where proteins such as NuMA (also known as NUMA1) orient division along the interphase long axis of the cell. However, little is known about how cells control spindle positioning in three-dimensional (3D) environments, such as early mammalian embryos and a variety of adult tissues. Here, we use mouse embryonic stem cells (ESCs), which grow in 3D colonies, as a model to investigate division in 3D. We observe that, at the periphery of 3D colonies, ESCs display high spindle mobility and divide asymmetrically. Our data suggest that enhanced spindle movements are due to unequal distribution of the cell-cell junction protein E-cadherin between future daughter cells. Interestingly, when cells progress towards differentiation, division becomes more symmetric, with more elongated shapes in metaphase and enhanced cortical NuMA recruitment in anaphase. Altogether, this study suggests that in 3D contexts, the geometry of the cell and its contacts with neighbors control division orientation and symmetry. This article has an associated First Person interview with the first author of the paper

Three-dimensional geometry controls division symmetry in stem cell colonies

Proper control of division orientation and symmetry, largely determined by spindle positioning, is essential to development and homeostasis. Spindle positioning has been extensively studied in cells dividing in two-dimensional (2D) environments and in epithelial tissues, where proteins such as NuMA (also known as NUMA1) orient division along the interphase long axis of the cell. However, little is known about how cells control spindle positioning in three-dimensional (3D) environments, such as early mammalian embryos and a variety of adult tissues. Here, we use mouse embryonic stem cells (ESCs), which grow in 3D colonies, as a model to investigate division in 3D. We observe that, at the periphery of 3D colonies, ESCs display high spindle mobility and divide asymmetrically. Our data suggest that enhanced spindle movements are due to unequal distribution of the cell–cell junction protein E-cadherin between future daughter cells. Interestingly, when cells progress towards differentiation, division becomes more symmetric, with more elongated shapes in metaphase and enhanced cortical NuMA recruitment in anaphase. Altogether, this study suggests that in 3D contexts, the geometry of the cell and its contacts with neighbors control division orientation and symmetry

Abscission Couples Cell Division to Embryonic Stem Cell Fate.

Cell fate transitions are key to development and homeostasis. It is thus essential to understand the cellular mechanisms controlling fate transitions. Cell division has been implicated in fate decisions in many stem cell types, including neuronal and epithelial progenitors. In other stem cells, such as embryonic stem (ES) cells, the role of division remains unclear. Here, we show that exit from naive pluripotency in mouse ES cells generally occurs after a division. We further show that exit timing is strongly correlated between sister cells, which remain connected by cytoplasmic bridges long after division, and that bridge abscission progressively accelerates as cells exit naive pluripotency. Finally, interfering with abscission impairs naive pluripotency exit, and artificially inducing abscission accelerates it. Altogether, our data indicate that a switch in the division machinery leading to faster abscission regulates pluripotency exit. Our study identifies abscission as a key cellular process coupling cell division to fate transitions

Cortical cell stiffness is independent of substrate mechanics

Cortical stiffness is an important cellular property that changes during migration, adhesion and growth. Previous atomic force microscopy (AFM) indentation measurements of cells cultured on deformable substrates have suggested that cells adapt their stiffness to that of their surroundings. Here we show that the force applied by AFM to a cell results in a significant deformation of the underlying substrate if this substrate is softer than the cell. This ‘soft substrate effect’ leads to an underestimation of a cell’s elastic modulus when analysing data using a standard Hertz model, as confirmed by finite element modelling and AFM measurements of calibrated polyacrylamide beads, microglial cells and fibroblasts. To account for this substrate deformation, we developed a ‘composite cell–substrate model’. Correcting for the substrate indentation revealed that cortical cell stiffness is largely independent of substrate mechanics, which has major implications for our interpretation of many physiological and pathological processes

Quantifying subcellular dynamics in apoptotic cells with two-dimensional Gabor filters

We demonstrate an optical Fourier filtering method which can be used to characterize subcellular morphology during dynamic cellular function. In this paper, our Fourier filters were based on two-dimensional Gabor elementary functions, which can be tuned to sense directly object size and orientation. We utilize this method to quantify changes in mitochondrial and nuclear structure during the first three hours of apoptosis. We find that the technique is sensitive to a decrease in particle orientation consistent with apoptosis-induced mitochondrial fragmentation. The scattering signal changes were less pronounced in the nucleus and the remainder of the cytoplasm. Particles in these regions were less oriented than mitochondria and did not change orientation significantly