Biophysics

A direct computational assessment of vinculin-actin unbinding kinetics reveals catch bonding behavior

1. Willmor J Peña Ccoa
2. Fatemah Mukadum
3. Aubin Ramon
4. Guillaume Stirnemann
5. Glen M Hocky

Reviewed by PREreview

Interplay of condensate material properties and chromatin heterogeneity governs nuclear condensate ripening

1. Deb Sankar Banerjee
2. Tafadzwa Chigumira
3. Rachel M Lackner
4. Josiah C Kratz
5. David M Chenoweth
6. Shiladitya Banerjee
7. Huaiying Zhang

• Curated by eLife

  eLife Assessment

  In this potentially valuable study, the authors employed in vivo experiments and theoretical modeling to study the growth dynamics of nuclear condensates. They observed that condensates can exhibit distinct growth modes, as dictated by the competition between condensate surface tension and local elasticity of chromatin. While the theoretical model appears to capture the experimental observations, the level of evidence supporting the proposed growth mechanism is incomplete due to, among other limitations, the multiple fitting parameters and poorly justified Neo-Hookean elasticity.

Reviewed by eLife

Determining accurate conformational ensembles of intrinsically disordered proteins at atomic resolution

1. Kaushik Borthakur
2. Thomas R. Sisk
3. Francesco P. Panei
4. Massimiliano Bonomi
5. Paul Robustelli

Reviewed by PREreview

How cancer-associated fibroblasts promote T-cell exclusion in human lung tumors: a physical perspective

1. Joseph Ackermann
2. Chiara Bernard
3. Philemon Sirven
4. Hélène Salmon
5. Massimiliano Fraldi
6. Martine Ben Amar

• Curated by eLife

  eLife Assessment

  This is a useful report of a spatially-extended model to study the complex interactions between immune cells, fibroblasts, and cancer cells, providing insights into how fibroblast activation can influence tumor progression. The model opens up new possibilities for studying fibroblast-driven effects in diverse settings, which is crucial for understanding potential tumor microenvironment manipulations that could enhance immunotherapy efficacy. While the results presented are solid and follow logically from the model's assumptions, some of these assumptions may require further validation, as they appear to oversimplify certain aspects in light of complex experimental findings, system geometry, and general principles of active matter research.

Reviewed by eLife

Enhanced bacterial chemotaxis in confined microchannels: Optimal performance in lane widths matching circular swimming radius

1. Caijuan Yue
2. Chi Zhang
3. Rongjing Zhang
4. Junhua Yuan

• Curated by eLife

  eLife Assessment

  This valuable study examines the effects of side-wall confinement on the chemotaxis of swimming bacteria in a shallow microfluidic channel. The authors present solid experimental evidence, combined with geometric analysis and numerical simulations of simplified models, showing that chemotaxis is enhanced when the distance between the side walls is comparable to the intrinsic radius of circular swimming near open surfaces. This study should be of interest to scientists specializing in bacteria-surface interactions.

Reviewed by eLife

Ab initio prediction of specific phospholipid complexes and membrane association of HIV-1 MPER antibodies by multi-scale simulations

1. Colleen Maillie
2. Jay Golden
3. Ian A Wilson
4. Andrew B Ward
5. Marco Mravic

• Curated by eLife

  eLife Assessment

  This valuable study reports multi-scale molecular dynamics simulations to investigate a class of highly potent antibodies that simultaneously engage with the HIV-1 Envelope trimer and the viral membrane. The work provides insights into how broadly neutralizing antibodies associate with lipids proximal to membrane-associated epitopes to drive neutralization. After extensive revision, the level of evidence is considered solid, although a quantitative assessment of the underlying energetics remain difficult to obtain.

Reviewed by eLife

A conformational fingerprint for amyloidogenic light chains

1. Cristina Paissoni
2. Sarita Puri
3. Luca Broggini
4. Manoj K Sriramoju
5. Martina Maritan
6. Rosaria Russo
7. Valentina Speranzini
8. Federico Ballabio
9. Mario Nuvolone
10. Giampaolo Merlini
11. Giovanni Palladini
12. Shang-Te Danny Hsu
13. Stefano Ricagno
14. Carlo Camilloni

• Curated by eLife

  eLife Assessment

  This important study identifies the "H-state" as a potential conformational marker distinguishing amyloidogenic from non-amyloidogenic light chains, addressing a critical problem in protein misfolding and amyloidosis. By combining advanced techniques such as small-angle X-ray scattering, molecular dynamics simulations, and H-D exchange mass spectrometry, the authors provide convincing evidence for their novel findings. However, incomplete experimental descriptions, limitations in SAXS data interpretation, and the way HDX MS data is presented affect the strength and generalizability of the conclusions. Strengthening these aspects would enhance the impact of this work for researchers in amyloidosis and protein misfolding.

Reviewed by eLife

Molecular dynamics simulations illuminate the role of sequence context in the ELF3-PrD-based temperature sensing mechanism in plants

1. Richard J Lindsay
2. Rafael Giordano Viegas
3. Vitor BP Leite
4. Philip A Wigge
5. Sonya M Hanson

• Curated by eLife

  eLife Assessment

  In this potentially valuable computational study, the authors conducted atomistic and coarse-grained simulations to probe the temperature-dependent phase behaviors of ELF3, a disordered component of the evening complex in plant. The results aim to highlight the role of polyQ tracts in modulating the temperature sensitivity. The level of evidence is considered incomplete, due to the lack of systematic calibration of the coarse-grained model and limited statistical uncertainty analysis, especially considering the relatively subtle nature of the differences due to temperature change.

Reviewed by eLife

Motor Clustering Enhances Kinesin-driven Vesicle Transport

1. Rui Jiang
2. Qingzhou Feng
3. Daguan Nong
4. You Jung Kang
5. David Sept
6. William O. Hancock

Reviewed by preLights

Reversing protonation of weakly basic drugs greatly enhances intracellular diffusion and decreases lysosomal sequestration

1. Debabrata Dey
2. Shir Marciano
3. Anna Poryvai
4. Ondřej Groborz
5. Lucie Wohlrábová
6. Tomás Slanina
7. Gideon Schreiber

• Curated by eLife

  eLife Assessment

  This is a valuable study on the diffusion rates of drug molecules in human-derived cells, presenting convincing data indicating that their diffusion behavior depends on their charged state. It proposes that blocking drug protonation enhances diffusion and fractional recovery, suggesting improved intracellular availability of weakly basic drugs. The findings are significant for drug design and understanding the biophysical behavior of small molecules in cells.

Reviewed by eLife