Biophysics

Collective directional memory controls the range of epithelial cell migration

1. Helena Canever
2. Hugo Lachuer
3. Quentin Delaunay
4. François Sipieter
5. Nicolas Audugé
6. Philippe P Girard
7. Nicolas Borghi

• Curated by eLife

  eLife Assessment

  The authors make the valuable observation that directional memory during epithelial cell migration is enhanced in collective contexts compared to single-cell migration. While there is solid evidence for some parts of the work, the evidence linking directional memory to adherens junctions and vinculin dimerization remains limited. Key issues are that the Y1065E mutant may affect vinculin beyond its ability to dimerize, and focal adhesions were not directly compared across migration contexts.

Reviewed by eLife

CFM: Confinement Force Microscopy—a dynamic, precise and stable microconfiner for traction force microscopy in spatial confinement

1. Fatemeh Abbasi
2. Katharina Rieck
3. Matthias Brandt
4. Maja Matis
5. Eva Kiermaier
6. Timo Betz

Reviewed by preLights

A comparative nanomechanical study of antibody and nanobody binding to SARS-CoV-2 variants

1. Luis F. Cofas-Vargas
2. Gustavo E. Olivos-Ramirez
3. Siewert J. Marrink
4. Adolfo B. Poma

Reviewed by PREreview

Thermodynamic principles of enzymatic regulation in biomolecular condensates from reaction-coupled molecular modeling

1. Enrico Lavagna
2. Francesco Delfino
3. Georgii Koniukov
4. Matteo Paloni
5. Luca Ciandrini
6. Alessandro Barducci

• Curated by eLife

  eLife assessment

  This study presents a reaction-coupled molecular simulation framework to investigate how enzymatic post-translational modifications regulate biomolecular condensates and where reactions preferentially occur within them. These findings are important, in particular, to the emergence of spatially heterogeneous reaction fluxes and enhanced activity at condensate interfaces. The work is timely and has implications beyond the immediate subfield, especially for understanding condensates as biochemical reaction centers. The strength of evidence is solid overall: the computational framework is well motivated and broadly supports the main conclusions, although some aspects of the model implementation, parameter choices, and controls would benefit from further clarification and validation.

Reviewed by eLife

Intracellular mechanical fingerprint reveals cell type-specific mechanical differences

1. Till M Muenker
2. Kerstin von Roden
3. Bart E Vos
4. Timo Betz

• Curated by eLife

  eLife Assessment

  Muenker and colleagues use an optical tweezer setup to apply oscillatory forces to endocytosed/phagocytosed glass beads over a wide frequency range (from ~1 to 1000 Hz) and probe cytoplasmic material properties at multiple time scales in six different cell types. Using statistical methods and principal component analysis, they find that the active and passive mechanical properties of cells can be described by 6 parameters (from power law fits) that allow characterizing the viscous and elastic nature of the cytoplasmic material as well as an effective active energy driven by cellular metabolism. Overall, this is a very well done and important work, using compelling and state-of-the-art methods.

Reviewed by eLife

Bifunctional architecture enables substrate catalysis and channeling in Paracoccus TMAO demethylase

1. Trung Thach
2. KanagaVijayan Dhanabalan
3. Shiwangi Maurya
4. Yu Han-Hallett
5. Senwei Quan
6. Jane Allison
7. Gurunath Ramanathan
8. Ramaswamy Subramanian

• Curated by eLife

  eLife Assessment

  This study reports high-resolution cryo-EM structures of Paracoccus trimethylamine N-oxide demethylase and advances the intriguing hypothesis that the enzyme may be bifunctional, coupling TMAO demethylation to formaldehyde capture at a distal tetrahydrofolate-binding site through an enclosed intramolecular tunnel. Supported by biochemical assays and molecular dynamics simulations, the structural findings are important and potentially of broad interest, particularly the unusual oligomeric architecture and the proposed conduit for a reactive intermediate. However, evidence that the conduit mediates formaldehyde channeling remains incomplete, because the current HCHO-THF measurements do not demonstrate enzyme-dependent transfer or distinguish downstream HCHO consumption from indirect effects of THF on enzyme activity.

Reviewed by eLife

Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons

1. Daniel Beaudet
2. Christopher L Berger
3. Adam G Hendricks

• Curated by eLife

  eLife Assessment

  In their important study, Beaudet, Berger and Hendricks provide a mechanistic link between disease-associated tau hyperphosphorylation, loss of cooperative tau envelope formation on microtubules, and dysregulation of axonal transport prior to aggregation. Using complementary in vitro reconstitution and human iPSC-derived neuronal assays with phosphodeficient and phosphomimetic tau constructs targeting 14 disease-relevant sites, the authors convincingly show that phosphorylation state alters tau organization on microtubules and differentially impacts kinesin- and lysosome-based transport. The evidence is solid and well aligned with the conclusions and will be of interest to the biophysical, cell biology and neurodegenerative communities.

Reviewed by eLife

A soft active matter models explains spiral epithelial cell migration on in-vivo corneas

1. Kaja Kostanjevec
2. Rastko Sknepnek
3. Jon Martin Collinson
4. Silke Henkes

• Curated by eLife

  eLife Assessment

  This useful study describes a physical mechanism for the emergence of spiral patterns in the outer epithelial layer of the mammalian cornea independent of pre-patterning or guidance cues, using an agent-based model of self-propelled particles with alignment. The well constructed model show that spiral patterns can emerge from the interaction between the limbus position, cell division, extrusion, and collective cell migration. While the conclusions are solid, some significant questions related to the importance of topological defect remain, and the comparison between the model and data are so far mostly qualitative.

Reviewed by eLife, preLights

Improved cryo-EM reconstruction of sub-50 kDa complexes using 2D template matching

1. Kexin Zhang
2. Timothy Grant
3. Nikolaus Grigorieff

• Curated by eLife

  eLife Assessment

  This important study builds on previous work from the same authors to present a conceptually distinct workflow for cryo-EM reconstruction that uses 2D template matching to enable high-resolution structure determination of small (sub-50 kDa) protein targets. The paper provides convincing evidence that the density for small-molecule ligands bound to such targets can be reconstructed without these ligands being present in the template, and it provides an insightful quantification of the level of model bias that remains in the resulting reconstructions. The convenient visualisation of small molecules bound to protein targets of a known structure will be relevant for the pharmaceutical industry.

Reviewed by eLife

Optimising the tilt increment for in situ cryo-electron tomography

1. Maarten Willem Tuijtel
2. Tomáš Majtner
3. Beata Turoňová
4. Martin Beck

• Curated by eLife

  eLife Assessment

  This convincing contribution addresses a question of practical importance: when collecting tilt-series data, what is the optimal angular step size between successive tilt images? The work provides valuable practical insights into cryo-ET data acquisition by demonstrating that balancing two competing demands - sufficient dose per individual tilt image and fine angular sampling - is essential to achieve high-quality tomographic reconstructions. They demonstrate that tilt-series acquired with finer increments (1-3 degrees) yield superior alignment accuracy and improved template-matching performance.

Reviewed by eLife