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1. Actomyosin dynamics modulate microtubule deformation and growth during T cell activation

   https://doi.org/10.1091/mbc.E20-10-0685  

   Rey-Suarez, Ivan; Rogers, Nate; Kerr, Sarah; Shroff, Hari; Upadhyaya, Arpita (January 2021, Molecular Biology of the Cell)

   Lidke, Diane S. (Ed.)

   Activation of T cells leads to the formation of the immunological synapse (IS) with antigen presenting cells. This requires T cell polarization and coordination between the actomyosin and microtubule cytoskeletons. The interactions between these two cytoskeletal components during T cell activation are not well understood. Here, we elucidate the interactions between microtubules and actin at the IS with high-resolution fluorescence microscopy. We show that microtubule growth dynamics in the peripheral actin-rich region are distinct from those in the central actin-free region. We further demonstrate that these differences arise from differential involvement of Arp2/3- and formin-nucleated actin structures. Formin inhibition results in a moderate decrease in microtubule growth rates, which is amplified in the presence of integrin engagement. In contrast, Arp2/3 inhibition leads to an increase in microtubule growth rates. We find that microtubule filaments are more deformed and exhibit greater shape fluctuations in the periphery of the IS compared to the center. Using small molecule inhibitors, we show that actin dynamics and actomyosin contractility play key roles in defining microtubule deformations and shape fluctuations. Our results indicate a mechanical coupling between the actomyosin and microtubule systems during T cell activation, whereby different actin structures influence microtubule dynamics in distinct ways. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] 

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2. Volumetric measurement of a Newtonian fluid flow through three-dimensional porous media using Lagrangian particle tracking (Shake-the-Box) technique

   https://doi.org/10.1063/5.0141535  

   Bagheri, Maryam; Mirbod, Parisa (April 2023, Physics of Fluids)

   This work experimentally investigates the pressure-driven flow of a pure Newtonian fluid through three-dimensional (3D) porous media models. The porous media model consists of square arrays of rods that also could be interpreted as a periodic tandem rod arrangement. We employed a time-resolved three-dimensional particle tracking velocimetry (3D Shake-the-Box) technique for a range of Reynolds numbers [Formula: see text] to observe flow structures and vortex formation between the rods in porous media structures with different porosities of [Formula: see text] which corresponds to the spacing ratio of [Formula: see text], where L is the distance between the centers of the rods, and D is the diameter of the rods. For all the examined cases, we further analyzed the effect of the Reynolds number and the spacing ratio on the instantaneous and averaged patterns of velocity, vorticity, and the other flow parameters after obtaining the two-dimensional velocity fields using the bin-averaging method. We observed both symmetrical and asymmetrical patterns of structure and recirculation regions between the rods depending on the Reynolds number and spacing ratio. Increasing the Reynolds number reduced the symmetrical patterns of flow structures with respect to the centerline of the gap region, while the spacing ratio was randomly affecting the symmetry degree. Vortex shedding was considerable for the two examined high Reynolds numbers of Re = 444 and Re = 890 behind the upstream rod as the porosity increased. The backward movement of the reattachment point has been observed by increasing the Reynolds number. 

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3. Local negative feedback of Rac activity at the leading edge underlies a pilot pseudopod-like program for amoeboid cell guidance

   https://doi.org/10.1371/journal.pbio.3002307  

   Town, Jason P.; Weiner, Orion D. (September 2023, PLOS Biology)

   Machesky, Laura (Ed.)

   To migrate efficiently, neutrophils must polarize their cytoskeletal regulators along a single axis of motion. This polarization process is thought to be mediated through local positive feedback that amplifies leading edge signals and global negative feedback that enables sites of positive feedback to compete for dominance. Though this two-component model efficiently establishes cell polarity, it has potential limitations, including a tendency to “lock” onto a particular direction, limiting the ability of cells to reorient. We use spatially defined optogenetic control of a leading edge organizer (PI3K) to probe how neutrophil-like HL-60 cells balance “decisiveness” needed to polarize in a single direction with the flexibility needed to respond to new cues. Underlying this balancing act is a local Rac inhibition process that destabilizes the leading edge to promote exploration. We show that this local inhibition enables cells to process input signal dynamics, linking front stability and orientation to local temporal increases in input signals. 

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4. Edge-Cuts of Optimal Average Weights

   https://doi.org/10.1142/S0217595919400062  

   Payne, Scott; Fuller, Edgar; Zhang, Cun-Quan (April 2019, Asia-Pacific Journal of Operational Research)

   Let [Formula: see text] be a directed graph associated with a weight [Formula: see text]. For an edge-cut [Formula: see text] of [Formula: see text], the average weight of [Formula: see text] is denoted and defined as [Formula: see text]. An optimal edge-cut with average weight is an edge-cut [Formula: see text] such that [Formula: see text] is maximum among all edge-cuts (or minimum, symmetrically). In this paper, a polynomial algorithm for this problem is proposed for finding an optimal edge-cut in a rooted tree separating the root and the set of all leafs. This algorithm enables us to develop an automatic clustering method with more accurate detection of community output. 

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5. Model supports asymmetric regulation across the intercellular junction for collective cell polarization

   https://doi.org/10.1371/journal.pcbi.1012216  

   Levandosky, Katherine; Copos, Calina (December 2024, PLOS Computational Biology)

   Vavylonis, Dimitrios (Ed.)

   Symmetry breaking, which is ubiquitous in biological cells, functionally enables directed cell movement and organized embryogenesis. Prior to movement, cells break symmetry to form a well-defined cell front and rear in a process called polarization. In developing and regenerating tissues, collective cell movement requires the coordination of the polarity of the migration machineries of neighboring cells. Though several works shed light on the molecular basis of polarity, fewer studies have focused on the regulation across the cell-cell junction required for collective polarization, thus limiting our ability to connect tissue-level dynamics to subcellular interactions. Here, we investigated how polarity signals are communicated from one cell to its neighbor to ensure coordinated front-to-rear symmetry breaking with the same orientation across the group. In a theoretical setting, we systematically searched a variety of intercellular interactions and identified that co-alignment arrangement of the polarity axes in groups of two and four cells can only be achieved with strong asymmetric regulation of Rho GTPases or enhanced assembly of complementary F-actin structures across the junction. Our results held if we further assumed the presence of an external stimulus, intrinsic cell-to-cell variability, or larger groups. The results underline the potential of using quantitative models to probe the molecular interactions required for macroscopic biological phenomena. Lastly, we posit that asymmetric regulation is achieved through junction proteins and predict that in the absence of cytoplasmic tails of such linker proteins, the likeliness of doublet co-polarity is greatly diminished. 

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