by Keyword: Require
Rossetti, Leone, Grosser, Steffen, Abenza, Juan Francisco, Valon, Leo, Roca-Cusachs, Pere, Alert, Ricard, Trepat, Xavier, (2024). Optogenetic generation of leader cells reveals a force-velocity relation for collective cell migration Nature Physics 20, 1659-1669
During development, wound healing and cancer invasion, migrating cell clusters feature highly protrusive leader cells at their front. Leader cells are thought to pull and direct their cohort of followers, but whether their local action is enough to guide the entire cluster, or if a global mechanical organization is needed, remains controversial. Here we show that the effectiveness of the leader-follower organization is proportional to the asymmetry of traction and tension within cell clusters. By combining hydrogel micropatterning and optogenetic activation, we generate highly protrusive leaders at the edge of minimal cell clusters. We find that the induced leader can robustly drag one follower but not larger groups. By measuring traction forces and tension propagation in clusters of increasing size, we establish a quantitative relationship between group velocity and the asymmetry of the traction and tension profiles. Modelling motile clusters as active polar fluids, we explain this force-velocity relationship in terms of asymmetries in the active traction profile. Our results challenge the notion of autonomous leader cells, showing that collective cell migration requires global mechanical organization within the cluster. Leader cells play an important role in guiding migratory clusters in various biological processes. Now, the mechanical organization of leader and followers within a cell cluster is shown to enable collective migration.
JTD Keywords: Driven, Dynamics, Guidance, Require
Monteil, VM, Wright, SC, Dyczynski, M, Kellner, MJ, Appelberg, S, Platzer, SW, Ibrahim, A, Kwon, H, Pittarokoilis, I, Mirandola, M, Michlits, G, Devignot, S, Elder, E, Abdurahman, S, Bereczky, S, Bagci, B, Youhanna, S, Aastrup, T, Lauschke, VM, Salata, C, Elaldi, N, Weber, F, Monserrat, N, Hawman, DW, Feldmann, H, Horn, M, Penninger, JM, Mirazimi, A, (2024). Crimean-Congo haemorrhagic fever virus uses LDLR to bind and enter host cells Nature Microbiology 9, 1499-1512 
Climate change and population densities accelerated transmission of highly pathogenic viruses to humans, including the Crimean-Congo haemorrhagic fever virus (CCHFV). Here we report that the Low Density Lipoprotein Receptor (LDLR) is a critical receptor for CCHFV cell entry, playing a vital role in CCHFV infection in cell culture and blood vessel organoids. The interaction between CCHFV and LDLR is highly specific, with other members of the LDLR protein family failing to bind to or neutralize the virus. Biosensor experiments demonstrate that LDLR specifically binds the surface glycoproteins of CCHFV. Importantly, mice lacking LDLR exhibit a delay in CCHFV-induced disease. Furthermore, we identified the presence of Apolipoprotein E (ApoE) on CCHFV particles. Our findings highlight the essential role of LDLR in CCHFV infection, irrespective of ApoE presence, when the virus is produced in tick cells. This discovery holds profound implications for the development of future therapies against CCHFV. Laboratory and clinical strains of Crimean-Congo haemorrhagic fever virus use LDLR to bind and enter host cells in blood vessel organoids and mice. Infection can also occur through ApoE, possibly present on virus particles.
JTD Keywords: Cholesterol, Clathrin, Entry requires, Genetics, Localization, Protei, Receptor
