Biophysics

Invasive cancer cells soften collagen networks and disrupt stress-stiffening via volume exclusion, contractility and adhesion

1. Irène Nagle
2. Margherita Tavasso
3. Ankur D. Bordoloi
4. Iain A.A. Muntz
5. Gijsje H. Koenderink
6. Pouyan E. Boukany

Reviewed by PREreview

Stall force measurement of the kinesin-3 motor KIF1A using a programmable DNA origami nanospring

1. Nobumichi Takamatsu
2. Hiroko Furumoto
3. Takayuki Ariga
4. Mitsuhiro Iwaki
5. Kumiko Hayashi

• Curated by eLife

  eLife Assessment

  Optical tweezers have been instrumental to the determination of mechanical parameters of molecular motors. This study by Takamatsu et al. reports key mechanical parameters of kinesin KIF1A using fluorescence microscopy, wherein the motor is tethered to a DNA nanospring, without the use of an optical trapping apparatus, which represents an exciting development. The approach and the findings reported change current thinking about KIF1A‑mediated transport, with potential implications for understanding human disease. The findings are important and the strength of the evidence is compelling.

Reviewed by eLife

Active regulation of the epidermal growth factor receptor by the membrane bilayer

1. Shwetha Srinivasan
2. Xingcheng Lin
3. Xuyan Chen
4. Raju Regmi
5. Bin Zhang
6. Gabriela S Schlau-Cohen

• Curated by eLife

  eLife Assessment

  The authors describe an interesting approach to studying the dynamics and function of membrane proteins in different lipid environments. The fundamental findings have theoretical and practical implications beyond the study of EGFR to all membrane signalling proteins. The evidence supporting the conclusions is compelling, based on the use of a nanodisk system to study membrane proteins in vitro, combined with state-of-the-art single-molecule FRET. The work will be of broad interest to cell biologists and biochemists.

Reviewed by eLife

Cluster size determines internal structure of transcription factories in human cells

1. Massimiliano Semeraro
2. Giuseppe Negro
3. Giada Forte
4. Antonio Suma
5. Giuseppe Gonnella
6. Peter R Cook
7. Davide Marenduzzo

• Curated by eLife

  eLife Assessment

  This is a valuable polymer model that provides insight into the origin of macromolecular mixed and demixed states within transcription clusters. The simulations are well performed and clearly presented in the context of existing experimental datasets. This compelling study will be of interest to those studying gene expression in the context of chromatin.

Reviewed by eLife

Effects of residue substitutions on the cellular abundance of proteins

1. Thea K Schulze
2. Kresten Lindorff-Larsen

• Curated by eLife

  eLife Assessment

  This valuable study presents a thorough analysis of protein abundance changes caused by amino acid substitutions, using structural context to improve predictive accuracy. By deriving substitution response matrices based on solvent accessibility, the authors demonstrate that simple structural features can predict abundance effects with accuracy comparable to complex methods such as free energy calculations. The strength of the evidence is convincing, supported by robust experimental design and comprehensive analyses.

Reviewed by eLife, PREreview

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 describes how density for small-molecule ligands bound to such targets can be reconstructed without these ligands being present in the template. However, the evidence described for the claim that this technique "significantly" improves the alignment of the reconstruction of small complexes is incomplete. The authors could better evaluate the effects of model bias on the reconstructed densities.

Reviewed by eLife

Allosteric effects of the coupling cation in melibiose transporter MelB

1. Parameswaran Hariharan
2. Yuqi Shi
3. Bakhtiiari Amirhossein
4. Ruibin Liang
5. Rosa Viner
6. Lan Guan

• Curated by eLife

  eLife Assessment

  This manuscript presents useful insights into the molecular basis underlying the positive cooperativity between the co-transported substrates (galactoside sugar and sodium ion) in the melibiose transporter MelB. Building on years of previous studies, this convincing study improves on the resolution of previously published structures and reports the presence of a water molecule in the sugar binding site that would appear to be key for its recognition, introduces further structures bound to different substrates, and utilizes binding and transport assays, as well as HDX-MS and molecular dynamics simulations to further understand the positive cooperativity between sugar and the co-transported sodium cation. The work will be of interest to biologists and biochemists working on cation-coupled symporters, which mediate the transport of a wide range of solutes across cell membranes.

Reviewed by eLife

A quantitative pipeline for whole-mount deep imaging and analysis of multi-layered organoids across scales

1. Alice Gros
2. Jules Vanaret
3. Valentin Dunsing-Eichenauer
4. Agathe Rostan
5. Philippe Roudot
6. Pierre-François Lenne
7. Léo Guignard
8. Sham Tlili

• Curated by eLife

  eLife Assessment

  This work describes the establishment of an image analysis pipeline for signal correction, segmentation and quantitative data analysis of multilayered organoid and tumoroid systems. The revised study is important for the field to address many practical challenges in deep-tissue visualization. The image analysis pipeline is well-designed and compelling.

Reviewed by eLife

Enhanced Processivity and Collective Force Production of Kinesin-1 at Low Radial Forces

1. Andrew M Hensley
2. Ahmet Yildiz

• Curated by eLife

  eLife Assessment

  The current work uses DNA-tethered motor trapping to reduce vertical forces and improve datasets for kinesin-1 motility under load. The evidence is compelling and the significance is important to the kinesin field. Kinesin-1 is more robust and less prone to premature detachment than previously indicated. This represents a significant advancement in the field and is generally applicable to work with optical tweezers.

Reviewed by eLife

Conformational Variability of HIV-1 Env Trimer and Viral Vulnerability

1. Yiwei Cao
2. Wonpil Im

• Curated by eLife

  eLife Assessment

  In this useful study, the authors conducted an impressive amount of atomistic simulations with a realistic asymmetric lipid bilayer to probe how the HIV-1 envelope glycoprotein (Env) transmembrane domain, cytoplasmic tail, and membrane environment influence ectodomain orientation and antibody epitope exposure. The simulations convincingly show that ectodomain motion is dominated by tilting relative to the membrane and explicitly demonstrate the role of membrane asymmetry in modulating the protein conformation and orientation. However, due to the qualitative nature of the conducted analyses, the evidence for the coupling between membrane-proximal regions and the antigenic surface is considered incomplete. With stronger integration of prior experimental and computational literature, this work has the potential to serve as a reference for how Env behaves in a realistic, glycosylated, membrane-embedded context.

Reviewed by eLife