Browsing by Author "Konstantopoulos, Konstantinos"

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    Experimental and theoretical model for the origin of coiling of cellular protrusions around fibers
    Sadhu, Raj Kumar; Hernandez-Padilla, Christian; Eisenbach, Samo Penič; Zhang, Lixia; Vishwasrao, Harshad D.; Behkam, Bahareh; Konstantopoulos, Konstantinos; Shroff, Hari; Iglič, Aleš; Peles, Elior; Nain, Amrinder S.; Gov, Nir S. (Nature Research, 2023-09-12)
    Protrusions at the leading-edge of a cell play an important role in sensing the extracellular cues during cellular spreading and motility. Recent studies provided indications that these protrusions wrap (coil) around the extracellular fibers. However, the physics of this coiling process, and the mechanisms that drive it, are not well understood. We present a combined theoretical and experimental study of the coiling of cellular protrusions on fibers of different geometry. Our theoretical model describes membrane protrusions that are produced by curved membrane proteins that recruit the protrusive forces of actin polymerization, and identifies the role of bending and adhesion energies in orienting the leading-edges of the protrusions along the azimuthal (coiling) direction. Our model predicts that the cell’s leading-edge coils on fibers with circular cross-section (above some critical radius), but the coiling ceases for flattened fibers of highly elliptical cross-section. These predictions are verified by 3D visualization and quantitation of coiling on suspended fibers using Dual- View light-sheet microscopy (diSPIM). Overall, we provide a theoretical framework, supported by experiments, which explains the physical origin of the coiling phenomenon.
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    Sculpting Rupture-Free Nuclear Shapes in Fibrous Environments
    Aniket, Jana; Tran, Avery; Gill, Amritpal; Kiepas, Alexander; Kapania, Rakesh K.; Konstantopoulos, Konstantinos; Nain, Amrinder S. (Wiley, 2022)
    Cytoskeleton-mediated force transmission regulates nucleus morphology. How nuclei shaping occurs in fibrous in vivo environments remains poorly understood. Here suspended nanofiber networks of precisely tunable (nm–μm) diameters are used to quantify nucleus plasticity in fibrous environments mimicking the natural extracellular matrix. Contrary to the apical cap over the nucleus in cells on 2-dimensional surfaces, the cytoskeleton of cells on fibers displays a uniform actin network caging the nucleus. The role of contractility-driven caging in sculpting nuclear shapes is investigated as cells spread on aligned single fibers, doublets, and multiple fibers of varying diameters. Cell contractility increases with fiber diameter due to increased focal adhesion clustering and density of actin stress fibers, which correlates with increased mechanosensitive transcription factor Yes-associated protein (YAP) translocation to the nucleus. Unexpectedly, large- and small-diameter fiber combinations lead to teardrop-shaped nuclei due to stress fiber anisotropy across the cell. As cells spread on fibers, diameter-dependent nuclear envelope invaginations that run the nucleus’s length are formed at fiber contact sites. The sharpest invaginations enriched with heterochromatin clustering and sites of DNA repair are insufficient to trigger nucleus rupture. Overall, the authors quantitate the previously unknown sculpting and adaptability of nuclei to fibrous environments with pathophysiological implications.