Biophysics

Protein phase change batteries drive innate immune signaling and cell fate

1. Alejandro Rodriguez Gama
2. Tayla Miller
3. Shriram Venkatesan
4. Jeffrey J Lange
5. Jianzheng Wu
6. Xiaoqing Song
7. Dan Bradford
8. Malcolm Cook
9. Jay R Unruh
10. Randal Halfmann

• Curated by eLife

  eLife Assessment

  This valuable study investigates the self-assembly activity of death-fold domains. The data collected using advanced microscopy and distributed amphifluoric FRET-based flow cytometry methods provide solid evidence for the conclusions, although the interpretations based on these conclusions remain speculative in some cases. This paper is broad interest to those studying a variety of biological pathways involved in inflammatory responses and various forms of cell death.

Reviewed by eLife

The cytoplasm of living cells can sustain transient and steady intracellular pressure gradients

1. Majid Malboubi
2. Mohammad Hadi Esteki
3. Malti B Vaghela
4. Lulu IT Korsak
5. Ryan J Petrie
6. Emad Moeendarbary
7. Guillaume Charras

• Curated by eLife

  eLife Assessment

  This important study combines imaginative and innovative experiments with a finite element modelling to demonstrate the relevance of poroelasticity in the mechanical properties of cells across physiologically relevant time and length scales. The authors present convincing evidence that cytosolic flows and pressure gradients can persist in cells with permeable membranes, generating spatially segregated influx and outflux zones. These findings are of interest to the cell biology and biophysics communities.

Reviewed by eLife

Allosteric effects of the coupling cation in melibiose transporter MelB

1. Parameswaran Hariharan
2. Yuqi Shi
3. Rosa Viner
4. 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 work 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 HDX-MS to further understand the positive cooperativity between sugar and the co-transported sodium cation. Although the experimental work is solid, the presentation of the data lacks clarity, and in particular, the HDX-MS data interpretation requires further explanation in both methodology and discussion, as well as a clearer description of the new insight that is obtained in relation to previous studies. 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

In silico design and validation of high-affinity RNA aptamers for SARS-CoV-2 comparable to neutralizing antibodies

1. Yanqing Yang
2. Lulu Qiao
3. Yangwei Jiang
4. Zhiye Wang
5. Dong Zhang
6. Damiano Buratto
7. Liquan Huang
8. Ruhong Zhou

• Curated by eLife

  eLife Assessment

  This study presents a computational-experimental workflow for optimizing RNA aptamers targeting SARS-CoV-2 RBD. While the integrated approach combining docking, molecular dynamics, and experimental validation shows some promise, the useful findings are limited by the extremely weak binding affinities (>100 µM KD) and restriction to a single target system. The evidence is incomplete, with experimental design issues in the antibody competition assays and a lack of specificity testing undermining confidence in the conclusions.

Reviewed by eLife

PARP1 inhibitors regulate PARP1 structure independent of DNA, reducing binding affinity for single strand breaks

1. Mark Pailing
2. Lotte van Beek
3. Taiana Maia de Oliveira
4. Maria M. Flocco
5. Bart W. Hoogenboom

Reviewed by Arcadia Science

Criticality-driven enhancer-promoter dynamics in Drosophila chromosomes

1. Gautham Ganesh
2. Jean-Bernard Fiche
3. Marcelo Nöllmann
4. Julien Mozziconacci

• Curated by eLife

  eLife Assessment

  This manuscript uses modeling approaches to provide mechanistic insight into the structural and dynamic properties of enhancer-promoter interactions in Drosophila. Given the interest in this field, this is a timely approach, and the results give useful insights by providing predictions about the processivity of cohesin loop extrusion in Drosophila and concluding that the compartmental interaction strength is poised near criticality in the coil-globule phase space. The evidence provided to support some of the conclusions is, however, incomplete and would be strengthened by better considering some of the caveats in the data used to constrain the models, such as the use of "homie" genetic elements in the dynamic data. There is insufficient evidence provided for the dynamics being criticality-driven, and in addition, consideration of alternative models would further strengthen the conclusions of the manuscript.

Reviewed by eLife

AF2χ: Predicting protein side-chain rotamer distributions with AlphaFold2

1. Matteo Cagiada
2. F. Emil Thomasen
3. Sergey Ovchinnikov
4. Charlotte M. Deane
5. Kresten Lindorff-Larsen

Reviewed by PREreview

Detecting directed motion and confinement in single-particle trajectories using hidden variables

1. François Simon
2. Guillaume Ramadier
3. Inès Fonquernie
4. Janka Zsok
5. Sergiy Patskovsky
6. Michel Meunier
7. Caroline Boudoux
8. Elisa Dultz
9. Lucien E Weiss

• Curated by eLife

  eLife Assessment

  In this valuable contribution, the authors present a novel and versatile probabilistic tool for classifying tracking behaviors and understanding parameters for different types of single-particle motion. The software package will be broadly applicable to single-particle tracking studies. The methodology has been convincingly tested by computational comparisons and experimental data, although the mathematical foundation for the hypothesis testing method can be further strengthened.

Reviewed by eLife

Multiphase separation in postsynaptic density regulated by membrane geometry via interaction valency and volume

1. Risa Yamada
2. Giovanni B Brandani
3. Shoji Takada

• Curated by eLife

  eLife Assessment

  This important study provides a conceptual advance in our understanding of how membrane geometry modulates the balance between specific and non-specific molecular interactions, reversing multiphase morphologies in postsynaptic protein assemblies. Using a mesoscale simulation framework grounded in experimental binding affinities, the authors successfully recapitulate key experimental observations in both solution and membrane-associated systems, providing novel mechanistic insight into how spatial constraints regulate postsynaptic condensate organization. The conclusions are supported by solid strength of evidence and the findings are of broad significance for both computational and experimental biologists

Reviewed by eLife

Differential interfacial tension between oncogenic and wild-type populations forms the mechanical basis of tissue-specific oncogenesis in epithelia

1. Amrapali Datta
2. Phanindra Dewan
3. Aswin Anto
4. Tanya Chhabra
5. Tanishq Tejaswi
6. Sindhu Muthukrishnan
7. Akshar Rao
8. Sumantra Sarkar
9. Medhavi Vishwakarma

• Curated by eLife

  eLife Assessment

  This important study reports that an oncogenic population in an epithelium can either be repressed or spread, depending on the tissues. This is explained based on the differential interfacial tension hypothesis, and supported by pharmacological perturbations and numerical simulations using the vertex model. The study conveys a key message, but, as it stands, the strength of evidence is incomplete, and a more detailed analysis of the mechanistic origin of the different tensions and better comparison between experiments and simulations would strongly strengthen the message.

Reviewed by eLife