Biophysics

Raman flow cytometry using time-delay integration

1. Matthew Lindley
2. Toshiki Kubo
3. Stéphanie Devineau
4. Menglu Li
5. Jing Qiao
6. Takuya Yashiro
7. Shiroh Iwanaga
8. Kazuyo Moro
9. Katsumasa Fujita

Reviewed by Arcadia Science

Responses to membrane potential-modulating ionic solutions measured by magnetic resonance imaging of cultured cells and in vivo rat cortex

1. Kyeongseon Min
2. Sungkwon Chung
3. Seung-Kyun Lee
4. Jongho Lee
5. Phan Tan Toi
6. Daehong Kim
7. Jung Seung Lee
8. Jang-Yeon Park

• Curated by eLife

  eLife Assessment

  The authors show MRI relaxation time changes that are claimed to originate from cell membrane potential changes. This would be a substantial contribution if true because it may provide a mechanism whereby membrane potential changes could be inferred noninvasively. However, the membrane potential manipulations applied here are performed on a slow time scale and are known to induce cell swelling. Cell swelling has been previously shown to affect relaxation time. Experiments could be performed to rule out this hypothesis, but the authors have chosen not to perform these experiments. The study is therefore useful, but the evidence is incomplete.

Reviewed by eLife

Scaling and merging macromolecular diffuse scattering with mdx2

1. Steve P. Meisburgera
2. Nozomi Andob

Reviewed by Arcadia Science

ATP-release pannexin channels are gated by lysophospholipids

1. Erik Henze
2. Russell N Burkhardt
3. Bennett William Fox
4. Tyler J Schwertfeger
5. Eric Gelsleichter
6. Kevin Michalski
7. Lydia Kramer
8. Margret Lenfest
9. Jordyn M Boesch
10. Hening Lin
11. Frank C Schroeder
12. Toshimitsu Kawate

• Curated by eLife

  eLife Assessment

  Pannexin (Panx) channels are a family of poorly understood large-pore channels that mediate the release of substrates like ATP from cells, yet the physiological stimuli that activate these channels remain poorly understood. The study by Henze et al. describes an elegant approach wherein activity-guided fractionation of mouse liver led to the discovery that lysophospholipids (LPCs) activate Panx1 and Panx2 channels expressed in cells or reconstituted into liposomes. The authors provide compelling evidence that LPC-mediated activation of Panx1 is involved in joint pain and that Panx1 channels are required for the established effects of LPC on inflammasome activation in monocytes, suggesting that Panx channels play a role in inflammatory pathways. Overall, this important study reports a previously unanticipated mechanism wherein LPCs directly activate Panx channels. The work will be of interest to scientists investigating phospholipids, Panx channels, purinergic signalling and inflammation.

  [Editors' note: this paper was reviewed and curated by Biophysics Colab]

• Curated by Biophysics Colab

  Evaluation Statement (5 February 2025)

  Pannexin (Panx) channels are a family of poorly understood large-pore channels that mediate the release of substrates like ATP from cells, yet the physiological stimuli that activate these channels remain poorly understood. The preprint by Henze et al. describes an elegant approach wherein activity-guided fractionation of mouse liver led to the discovery that lysophospholipids (LPCs) activate Panx1 and Panx2 channels expressed in cells or reconstituted into liposomes. The authors provide evidence that LPC-mediated activation of Panx1 is involved in joint pain and that Panx1 channels are required for the established effects of LPC on inflammasome activation in monocytes, suggesting that Panx channels play a role in inflammatory pathways. Overall, this important study reports a previously unanticipated mechanism wherein LPCs directly activate Panx channels.

  Biophysics Colab recommends this study to scientists investigating phospholipids, Panx channels, purinergic signalling and inflammation.

  Biophysics Colab has evaluated this study as one that meets the following criteria:

  • Rigorous methodology
  • Transparent reporting
  • Appropriate interpretation

  (This evaluation refers to version 3 of this preprint, which has been revised in response to peer review of versions 1 and 2.)

Reviewed by eLife, Biophysics Colab

A mathematical model clarifies the ABC Score formula used in enhancer-gene prediction

1. Joseph Nasser
2. Kee-Myoung Nam
3. Jeremy Gunawardena

• Curated by eLife

  eLife Assessment

  This important study dissects the mathematical and biological assumptions underlying the commonly used Activity-by-Contact model of enhancer action in transcriptional regulation. The authors provide a convincing mathematical analysis that links this (mostly phenomenological) model to concrete molecular mechanisms of enhancer function. This work provides a strong foundation from which to analyze a broad swath of genome-wide data such as that generated by CRISPRi screens.

Reviewed by eLife

Geometry effects on protein mobility in a synapse

1. Simon Dannenberg
2. Sofiia Reshetniak
3. Sarah Mohammadinejad
4. Silvio O. Rizzoli
5. Stefan Klumpp

Reviewed by PREreview

Arp2/3-mediated bidirectional actin assembly by SPIN90 dimers in metazoans

1. Tianyang Liu
2. Luyan Cao
3. Miroslav Mladenov
4. Guillaume Romet-Lemonne
5. Michael Way
6. Carolyn A. Moores

Reviewed by Arcadia Science

The mechanism of DRB7.2:DRB4 mediated sequestering of endogenous inverted-repeat dsRNA precursors in plants

1. Sneha Paturi
2. Debadutta Patra
3. Priti Chanda Behera
4. Ramdas Aute
5. Nilam Waghela
6. Priyadarshan Kinatukara
7. Mandar V Deshmukh

• Curated by eLife

  eLife Assessment

  The manuscript provides valuable findings in the field for understanding the RNAi regulation in plants at the molecular level with a model of how DRB7.2 and DRB4 form a heterodimer and protect dsRNA from DICER activity. The presented data provide a solid basis for the model, but certain measurements could benefit from replicates for robust statistics.

Reviewed by eLife

Kinetic regulation of kinesin’s two motor domains coordinates its stepping along microtubules

1. Yamato Niitani
2. Kohei Matsuzaki
3. Erik Jonsson
4. Ronald D Vale
5. Michio Tomishige

• Curated by eLife

  eLife Assessment

  This study provides compelling evidence that kinesin's stepping mechanism is governed by strain-induced conformational changes in its nucleotide-binding pockets. Using pre-steady state kinetics and single-molecule assays, the authors demonstrate that the neck linker's conformation differentially modulates nucleotide affinity and detachment rates, establishing an asynchronous chemo-mechanical cycle that prevents simultaneous detachment. Supported by cryo-EM structural data, the work presents an important advance in our understanding of kinesin's hand-over-hand movement.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife, Review Commons

Characterization and modulation of human insulin degrading enzyme conformational dynamics to control enzyme activity

1. Jordan M Mancl
2. Wenguang G Liang
3. Nicholas L Bayhi
4. Hui Wei
5. Bridget Carragher
6. Clinton S Potter
7. Wei-Jen Tang

• Curated by eLife

  eLife Assessment

  The manuscript by Mancl et al. provides important mechanistic insights into the conformational dynamics of Insulin Degrading Enzyme (IDE), a zinc metalloprotease involved in the clearance of amyloid peptides. In the revised version, the authors have substantially expanded their analysis by incorporating time-resolved cryo-EM and coarse-grained molecular dynamics simulations, which reveal an insulin-induced allosteric transition and transient β-sheet interactions underlying IDE's unfoldase activity. Supported by a convincing combination of cryo-EM, SEC-SAXS, enzymatic assays, and both all-atom and coarse-grained simulations, this work refines our understanding of IDE's functional cycle and offers a structural framework for developing substrate-selective modulators of M16 metalloproteases.

Reviewed by eLife