Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion.

• MeSH
• buňky stromatu * MeSH
• fibroblasty MeSH
• lymfatické uzliny * MeSH
• lymfocyty MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.

• Klíčová slova
• T cells, Wiskott-Aldrich syndrome protein, actin cytoskeleton, ameboid motility, cell migration, confinement, dendritic cells, leukocytes, mechanical load, mechanosensing,
• MeSH
• aktiny metabolismus   fyziologie   MeSH
• biomechanika fyziologie   MeSH
• buněčné linie MeSH
• cytoskeletální proteiny metabolismus   MeSH
• komplex proteinů 2-3 souvisejících s aktinem metabolismus   fyziologie   MeSH
• leukocyty fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• pohyb buněk fyziologie   MeSH
• protein 3 související s aktinem metabolismus   MeSH
• protein Wiskottova-Aldrichova syndromu genetika   metabolismus   MeSH
• vazba proteinů fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aktiny MeSH
• cytoskeletální proteiny MeSH
• komplex proteinů 2-3 souvisejících s aktinem MeSH
• protein 3 související s aktinem MeSH
• protein Wiskottova-Aldrichova syndromu MeSH

Cell production and differentiation for the acquisition of specific functions are key features of living systems. The dynamic network of cellular microtubules provides the necessary platform to accommodate processes associated with the transition of cells through the individual phases of cytogenesis. Here, we show that the plant hormone cytokinin fine-tunes the activity of the microtubular cytoskeleton during cell differentiation and counteracts microtubular rearrangements driven by the hormone auxin. The endogenous upward gradient of cytokinin activity along the longitudinal growth axis in Arabidopsis thaliana roots correlates with robust rearrangements of the microtubule cytoskeleton in epidermal cells progressing from the proliferative to the differentiation stage. Controlled increases in cytokinin activity result in premature re-organization of the microtubule network from transversal to an oblique disposition in cells prior to their differentiation, whereas attenuated hormone perception delays cytoskeleton conversion into a configuration typical for differentiated cells. Intriguingly, cytokinin can interfere with microtubules also in animal cells, such as leukocytes, suggesting that a cytokinin-sensitive control pathway for the microtubular cytoskeleton may be at least partially conserved between plant and animal cells.

• Klíčová slova
• cell differentiation, cytokinin, cytoskeleton, microtubules, microtubules dynamics,
• MeSH
• Arabidopsis genetika   růst a vývoj   MeSH
• buněčná diferenciace * MeSH
• cytokininy genetika   metabolismus   MeSH
• kořeny rostlin genetika   růst a vývoj   MeSH
• mikrotubuly genetika   metabolismus   MeSH
• proliferace buněk * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokininy MeSH

Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force coupling is usually mediated by transmembrane adhesion receptors, especially those of the integrin family, amoeboid cells such as leukocytes can migrate extremely fast despite very low adhesive forces1. Here we show that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographical features of the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating retrograde shear forces that are sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent migration are not mutually exclusive, but rather are variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate interchangeably and simultaneously. As adhesion-free migration is independent of the chemical composition of the environment, it renders cells completely autonomous in their locomotive behaviour.

• MeSH
• aktiny metabolismus   MeSH
• buněčná adheze MeSH
• buněčné linie MeSH
• buněčné mikroprostředí * MeSH
• lidé MeSH
• mikrofilamenta metabolismus   MeSH
• myši MeSH
• pohyb buněk * MeSH
• T-lymfocyty cytologie   metabolismus   MeSH
• talin nedostatek   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aktiny MeSH
• talin MeSH