Biology subjects

Gov, N.

Publications and source records attributed to Gov, N..

23 records · Page 2Linked to original sources

bioRxiv2020

Tissue topography steers migrating Drosophila border cells

Moving cells can sense and respond to physical features of the microenvironment, however in vivo the significance of tissue topography is mostly unknown. Here we use the Drosophila border cells, an established model for in vivo cell migration, to study how chemical and physical information influence migration path selection. Live imaging, genetics, modeling, and simulations show that, although chemical cues were thought to be sufficient, microtopography is also important. Chemoattractants promote predominantly posterior movement, whereas tissue architecture presents orthogonal information, a path of least resistance concentrated near the center of the egg chamber. E-cadherin supplies a permissive haptotactic cue. Our results provide insight into how cells integrate and prioritize topographical, adhesive, and chemoattractant cues to choose one path amongst many.

developmental biology↗

bioRxiv2020

Cell substrate patterns driven by curvature-sensitive actin polymerization: waves and podosomes.

Cells adhered to an external solid substrate are observed to exhibit rich dynamics of actin structures on the basal membrane, which are distinct from those observed on the dorsal (free) membrane. Here we explore the dynamics of curved membrane proteins, or protein complexes, that recruit actin polymerization when the membrane is confined by the solid substrate. Such curved proteins can induce the spontaneous formation of membrane protrusions on the dorsal side of cells. However, on the basal side of the cells, such protrusions can only extend as far as the solid substrate and this constraint can convert such protrusions into propagating wave-like structures. We also demonstrate that adhesion molecules can stabilize localized protrusions, that resemble some features of podosomes. This coupling of curvature and actin forces may underlie the differences in the observed actin-membrane dynamics between the basal and dorsal sides of adhered cells.

biophysics↗

bioRxiv2019

Centering based on active diffusion in mouse oocytes is non-specific

The mechanism for nucleus centering in mouse oocytes results from a gradient of actin-positive vesicles. By microinjecting oil droplets and fluorescent beads, we analyze the consequences of the gradient of activity on transport of exogenous tracer particles of different sizes. We also use optical tweezers to probe rheological properties of the cytoplasm. We find that the gradient activity induces a general centering force, akin to an effective pressure gradient, leading to centering of oil droplets with velocities comparable to nuclear ones. High temporal resolution measurements reveal that passive particles, larger than 1{micro}m, experience the activity gradient by a biased diffusion towards the cell center. Unexpectedly, this general and size dependent mechanism is maintained in Meiosis I but contrasted by a further process that specifically off-centers the spindle. These antagonizing processes depend on myosin activity, thus we reconcile how the same molecular actors can have two opposite functions (centering versus off-centering).

cell biology↗

bioRxiv2018

Cell-extrinsic mechanical forces restore neutrophil polarization in the absence of branched actin assembly

Migratory cells use distinct motility modes to navigate different microenvironments, but it is unclear whether these modes rely on the same core set of polarity components. To investigate this, we disrupted Arp2/3 and WAVE complex, which assemble branched actin networks that are essential for neutrophil polarity and motility in standard adherent conditions. Surprisingly, confinement rescues polarity and movement of neutrophils lacking these components, revealing a processive bleb-based protrusion program that is mechanistically distinct from the branched actin-based protrusion program but shares some of the same core components and underlying molecular logic. We further find that the restriction of protrusion growth to one site does not always respond to membrane tension directly, as previously thought, but may rely on closely linked properties such as local membrane curvature. Our work reveals a hidden circuit for neutrophil polarity and indicates that cells have distinct molecular mechanisms for polarization that dominate in different microenvironments.

cell biology↗

bioRxiv2018

Both cell-intrinsic and environmental factors constrain speed and persistence in T cell migration

Cell migration is astoundingly diverse. Molecular signatures, cell-cell and cell-matrix interactions, and environmental structures each play their part in shaping cell motion, yielding numerous different cell morphologies and migration modes. Nevertheless, in recent years, a simple unifying law was found to describe cell migration across many different cell types and contexts: faster cells turn less frequently. Given this universal coupling between speed and persistence (UCSP), from a modelling perspective it is important to know whether computational models of cell migration capture this speed-persistence link. Here, we present an in-depth characterisation of an existing Cellular Potts Model (CPM). We first show that this model robustly reproduces the UCSP without having been designed for this task. Instead, we show that this fundamental law of migration emerges spontaneously through a crosstalk of intracellular mechanisms, cell shape, and environmental constraints, resembling the dynamic nature of cell migration in vivo. Our model also reveals how cell shape dynamics can further constrain cell motility by limiting both the speed and persistence a cell can reach, and how a rigid environment such as the skin can restrict cell motility even further. Our results further validate the CPM as a model of cell migration, and shed new light on the speed-persistence coupling that has emerged as a fundamental property of migrating cells. SIGNIFICANCEThe universal coupling between speed and persistence (UCSP) is the first general quantitative law describing motility patterns across the versatile spectrum of migrating cells. Here, we show - for the first time - that this migration law emerges spontaneously in an existing, highly popular computational model of cell migration. Studying the UCSP in entirely different model frameworks, not explicitly built with this law in mind, can help uncover how intracellular dynamics, cell shape, and environment interact to produce the diverse motility patterns observed in migrating cells.

immunology↗