@article{7623, abstract = {A two-dimensional mathematical model for cells migrating without adhesion capabilities is presented and analyzed. Cells are represented by their cortex, which is modeled as an elastic curve, subject to an internal pressure force. Net polymerization or depolymerization in the cortex is modeled via local addition or removal of material, driving a cortical flow. The model takes the form of a fully nonlinear degenerate parabolic system. An existence analysis is carried out by adapting ideas from the theory of gradient flows. Numerical simulations show that these simple rules can account for the behavior observed in experiments, suggesting a possible mechanical mechanism for adhesion-independent motility.}, author = {Jankowiak, Gaspard and Peurichard, Diane and Reversat, Anne and Schmeiser, Christian and Sixt, Michael K}, issn = {02182025}, journal = {Mathematical Models and Methods in Applied Sciences}, number = {3}, pages = {513--537}, publisher = {World Scientific}, title = {{Modeling adhesion-independent cell migration}}, doi = {10.1142/S021820252050013X}, volume = {30}, year = {2020}, } @article{7875, abstract = {Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic cells, local microtubule depolymerization within protrusions remote from the microtubule organizing center triggers actomyosin contractility controlled by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: (1) impaired cell edge coordination during path finding and (2) defective adhesion resolution. Compromised shape control is particularly hindering in geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. We thus demonstrate that microtubules can act as a proprioceptive device: they sense cell shape and control actomyosin retraction to sustain cellular coherence.}, author = {Kopf, Aglaja and Renkawitz, Jörg and Hauschild, Robert and Girkontaite, Irute and Tedford, Kerry and Merrin, Jack and Thorn-Seshold, Oliver and Trauner, Dirk and Häcker, Hans and Fischer, Klaus Dieter and Kiermaier, Eva and Sixt, Michael K}, issn = {1540-8140}, journal = {The Journal of Cell Biology}, number = {6}, publisher = {Rockefeller University Press}, title = {{Microtubules control cellular shape and coherence in amoeboid migrating cells}}, doi = {10.1083/jcb.201907154}, volume = {219}, year = {2020}, } @article{7876, abstract = {In contrast to lymph nodes, the lymphoid regions of the spleen—the white pulp—are located deep within the organ, yielding the trafficking paths of T cells in the white pulp largely invisible. In an intravital microscopy tour de force reported in this issue of Immunity, Chauveau et al. show that T cells perform unidirectional, perivascular migration through the enigmatic marginal zone bridging channels. }, author = {Sixt, Michael K and Lämmermann, Tim}, issn = {10974180}, journal = {Immunity}, number = {5}, pages = {721--723}, publisher = {Elsevier}, title = {{T cells: Bridge-and-channel commute to the white pulp}}, doi = {10.1016/j.immuni.2020.04.020}, volume = {52}, year = {2020}, } @article{7909, abstract = {Cell migration entails networks and bundles of actin filaments termed lamellipodia and microspikes or filopodia, respectively, as well as focal adhesions, all of which recruit Ena/VASP family members hitherto thought to antagonize efficient cell motility. However, we find these proteins to act as positive regulators of migration in different murine cell lines. CRISPR/Cas9-mediated loss of Ena/VASP proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture, as evidenced by changed network geometry as well as reduction of filament length and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping protein accumulation. Loss of Ena/VASP function also abolished the formation of microspikes normally embedded in lamellipodia, but not of filopodia capable of emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated adhesion accompanied by reduced traction forces exerted through these structures. Our data thus uncover novel Ena/VASP functions of these actin polymerases that are fully consistent with their promotion of cell migration.}, author = {Damiano-Guercio, Julia and Kurzawa, Laëtitia and Müller, Jan and Dimchev, Georgi A and Schaks, Matthias and Nemethova, Maria and Pokrant, Thomas and Brühmann, Stefan and Linkner, Joern and Blanchoin, Laurent and Sixt, Michael K and Rottner, Klemens and Faix, Jan}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion}}, doi = {10.7554/eLife.55351}, volume = {9}, year = {2020}, } @article{8132, abstract = {The WAVE regulatory complex (WRC) is crucial for assembly of the peripheral branched actin network constituting one of the main drivers of eukaryotic cell migration. Here, we uncover an essential role of the hematopoietic-specific WRC component HEM1 for immune cell development. Germline-encoded HEM1 deficiency underlies an inborn error of immunity with systemic autoimmunity, at cellular level marked by WRC destabilization, reduced filamentous actin, and failure to assemble lamellipodia. Hem1−/− mice display systemic autoimmunity, phenocopying the human disease. In the absence of Hem1, B cells become deprived of extracellular stimuli necessary to maintain the strength of B cell receptor signaling at a level permissive for survival of non-autoreactive B cells. This shifts the balance of B cell fate choices toward autoreactive B cells and thus autoimmunity.}, author = {Salzer, Elisabeth and Zoghi, Samaneh and Kiss, Máté G. and Kage, Frieda and Rashkova, Christina and Stahnke, Stephanie and Haimel, Matthias and Platzer, René and Caldera, Michael and Ardy, Rico Chandra and Hoeger, Birgit and Block, Jana and Medgyesi, David and Sin, Celine and Shahkarami, Sepideh and Kain, Renate and Ziaee, Vahid and Hammerl, Peter and Bock, Christoph and Menche, Jörg and Dupré, Loïc and Huppa, Johannes B. and Sixt, Michael K and Lomakin, Alexis and Rottner, Klemens and Binder, Christoph J. and Stradal, Theresia E.B. and Rezaei, Nima and Boztug, Kaan}, issn = {24709468}, journal = {Science Immunology}, number = {49}, publisher = {AAAS}, title = {{The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity}}, doi = {10.1126/sciimmunol.abc3979}, volume = {5}, year = {2020}, } @article{8787, abstract = {Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets.}, author = {Nicolai, Leo and Schiefelbein, Karin and Lipsky, Silvia and Leunig, Alexander and Hoffknecht, Marie and Pekayvaz, Kami and Raude, Ben and Marx, Charlotte and Ehrlich, Andreas and Pircher, Joachim and Zhang, Zhe and Saleh, Inas and Marel, Anna-Kristina and Löf, Achim and Petzold, Tobias and Lorenz, Michael and Stark, Konstantin and Pick, Robert and Rosenberger, Gerhild and Weckbach, Ludwig and Uhl, Bernd and Xia, Sheng and Reichel, Christoph Andreas and Walzog, Barbara and Schulz, Christian and Zheden, Vanessa and Bender, Markus and Li, Rong and Massberg, Steffen and Gärtner, Florian R}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Vascular surveillance by haptotactic blood platelets in inflammation and infection}}, doi = {10.1038/s41467-020-19515-0}, volume = {11}, year = {2020}, } @article{8142, abstract = {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.}, author = {Montesinos López, Juan C and Abuzeineh, A and Kopf, Aglaja and Juanes Garcia, Alba and Ötvös, Krisztina and Petrášek, J and Sixt, Michael K and Benková, Eva}, issn = {1460-2075}, journal = {The Embo Journal}, number = {17}, publisher = {Embo Press}, title = {{Phytohormone cytokinin guides microtubule dynamics during cell progression from proliferative to differentiated stage}}, doi = {10.15252/embj.2019104238}, volume = {39}, year = {2020}, } @article{7885, abstract = {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.}, author = {Reversat, Anne and Gärtner, Florian R and Merrin, Jack and Stopp, Julian A and Tasciyan, Saren and Aguilera Servin, Juan L and De Vries, Ingrid and Hauschild, Robert and Hons, Miroslav and Piel, Matthieu and Callan-Jones, Andrew and Voituriez, Raphael and Sixt, Michael K}, issn = {14764687}, journal = {Nature}, pages = {582–585}, publisher = {Springer Nature}, title = {{Cellular locomotion using environmental topography}}, doi = {10.1038/s41586-020-2283-z}, volume = {582}, year = {2020}, } @article{8190, author = {Sixt, Michael K and Huttenlocher, Anna}, issn = {1540-8140}, journal = {The Journal of Cell Biology}, number = {8}, publisher = {Rockefeller University Press}, title = {{Zena Werb (1945-2020): Cell biology in context}}, doi = {10.1083/jcb.202007029}, volume = {219}, year = {2020}, } @article{6824, abstract = {Platelets are small anucleate cellular fragments that are released by megakaryocytes and safeguard vascular integrity through a process termed ‘haemostasis’. However, platelets have important roles beyond haemostasis as they contribute to the initiation and coordination of intravascular immune responses. They continuously monitor blood vessel integrity and tightly coordinate vascular trafficking and functions of multiple cell types. In this way platelets act as ‘patrolling officers of the vascular highway’ that help to establish effective immune responses to infections and cancer. Here we discuss the distinct biological features of platelets that allow them to shape immune responses to pathogens and tumour cells, highlighting the parallels between these responses.}, author = {Gärtner, Florian R and Massberg, Steffen}, issn = {1474-1741}, journal = {Nature Reviews Immunology}, number = {12}, pages = {747–760}, publisher = {Springer Nature}, title = {{Patrolling the vascular borders: Platelets in immunity to infection and cancer}}, doi = {10.1038/s41577-019-0202-z}, volume = {19}, year = {2019}, }