March in preprints – the CellBio edition

Cancer biology

Differential AXL expression and regulation of Arf1 controls matrix stiffness-dependent Golgi organization and function in breast cancer cells

Arnav Saha, Tushar Sherkhane, Nagaraj Balasubramanian

https://www.biorxiv.org/content/10.1101/2025.02.21.639478v1

Integrin-mediated cell-matrix adhesion regulates cell growth and survival, often disrupted in cancer cells, leading to anchorage independence. AXL, a receptor involved in rigidity sensing, regulates Golgi organization via Arf1 activation in a stiffness-dependent manner, affecting cell spreading, highlighting the AXL-Arf1-Golgi pathway’s role in cancer progression.

Picked by: Vibha Singh

Glioblastoma stem cell morphotypes convey distinct cell states and clinically relevant functions

Carlotta Barelli, Matteo Bonfanti, Filippo Mirabella, Dario Ricca, Negin Alizadehmohajer, Viktoria Sokolova, Alberto Campione, Giovanni M. Sicuri, Clelia Peano, Stefania Faletti, Roberto Stefini, Nereo Kalebic

https://www.biorxiv.org/content/10.1101/2025.03.24.644884v1

This preprint tries to link stem cell morphology and function, in the context of Glioblastoma stem cells (GSC), using patient-derived GSC organoids. Various morphologies of the organoids have distinct transcriptomic signatures which might indicate distinct requirements for anti-cancer treatment strategies.

Picked by: Girish Kale

Optogenetic stimulation of Lbc GEF-mediated Rho activity dynamics promotes cell invasion

Jessica Wagner, Konstantina Feller, Nicole Schrenke, Nina Schulze, Annette Paschen, Leif Dehmelt, Perihan Nalbant

https://www.biorxiv.org/content/10.1101/2025.03.28.646036v1

Unravelling the mechanisms behind cancer cell invasion is essential for developing targeted therapies to hinder tumor progression. This study provides insights about role of GEF-H1, an Lbc GEF, in promoting cancer cell invasion by dynamically modulating cell contraction forces. These research advances our understanding of the oncogenic functions of Lbc GEFs and provide a mechanistic framework for how cell contraction dynamics contribute to tumor invasion.

Picked by: Vibha Singh

From Wagner et al. (2025). This image is made available under a CC-BY-NC 4.0 International license.

Receptor tyrosine kinase AXL regulates Golgi organization and function through an adhesion-Arf1 signaling axis in breast and lung cancers

Prachi Joshi, Arnav Saha, Radhika Malaviya, Debiprasad Panda, Grishma Mehta, Manojeet Pattanayak, Vibha Singh, Nagaraj Balasubramanian

https://www.biorxiv.org/content/10.1101/2025.02.21.639453v1

Cell-matrix adhesion influences Golgi organization, and its disruption in cancer cells affects membrane trafficking and cargo processing. A screen identified different Golgi organization patterns in breast and lung cancer cells (MDAMB231 vs MCF7, A549 vs CaLu1), regulated by adhesion. In silico analysis linked receptor tyrosine kinase, AXL, to Golgi regulation. These findings validate AXL-Arf1 crosstalk as a key mediator of Golgi organization and function in cancer cells.

Picked by: Vibha Singh

Cell migration

Magnetotactic Bacteria Optimally Navigate Natural Pore Networks

Alexander P. Petroff, Julia Hernandez, Vladislav Kelin, Nina Radchenko-Hannafin

https://www.biorxiv.org/content/10.1101/2024.11.04.621871v2

This preprint focuses on bacteria that naturally respond to geomagnetic fields and asks how they use the geomagnetic field to navigate the natural obstacles these bacteria might experience. It uses an artificial magnetic field and pore space to figure out the optimal conditions for magnetotaxis across various magneto-sensing bacterial species.

Picked by: Girish Kale

From Petroff et al. (2025). This image is made available under a CC-BY 4.0 International license.

Corrections in single cell migration path in vivo are controlled by pulses in polar Rac1 activation

Dennis Hoffmann, Tal Agranov, Lucas Kühl, Benjamin D. Simons, Nir Gov, Erez Raz

https://www.biorxiv.org/content/10.1101/2025.02.24.639819v1

This study identifies that the pulsating Rac1 signalling network regulates periodic variations between run-and-tumble migration mode in zebrafish germ cells by driving Rac1 activity and actin polymerization. This mechanism ensures precise cell migration by removing previous polarity through apolar blebbing, emphasizing its importance in developmental processes and directed migration.

Picked by: Vibha Singh

Primordial germ cells experience increasing physical confinement and DNA damage during migration in the mouse embryo

Katharine Goodwin, Theresa Anne Emrich, Sebastian Arnold, Katie McDole

https://www.biorxiv.org/content/10.1101/2025.03.03.641275v1

Girish: This work presents evidence of an in vivo risk to genome integrity, with implications for DNA repair and adaptations to nuclear mechanics. The study focuses on Primordial Germ Cells, which give rise to sperm or egg, highlighting the mechanisms employed in cells where genome integrity is of paramount importance.

Sristi: This study is the first to capture the migratory behavior of mammalian primordial germ cells (PGC) from their origin to their target destination, the future gonad. As they traverse diverse cellular environments, PGCs encounter a variety of ECM conditions and physical constraints. Adapting to these changing surroundings, they exhibit dynamic changes in nuclear shapes, while maintaining a consistent migration strategy.

Picked by: Girish Kale & Sristilekha Nath

Cell organelles and organisation

Tubulin isotypes polymerise into sectioned microtubules that locally regulate protein binding

Manjari Prakash, Yean Ming Chew, Denisa Ondruskova, Jiri Miksatko, Alica Dodokova, Arya Krishnan, Carsten Janke, Robert A. Cross, Zdenek Lansky, Marcus Braun

https://www.biorxiv.org/content/10.1101/2025.03.12.642813v2

There are multiple genes encoding different tubulins, but how these different isoforms affect microtubule structure and behaviour isn’t fully understood. This study reveals that co-polymerisation of two different tubulin isoforms causes sectioning of microtubules with differing protofilament numbers and causes differential binding of microtubule-associated proteins.

Picked by: Matthew Davies

Quantitative intra-Golgi transport and organization data suggest the stable compartment nature of the Golgi

Hieng Chiong Tie, Haiyun Wang, Divyanshu Mahajan, Hilbert Yuen In Lam, Xiuping Sun, Bing Chen, Yuguang Mu, Lei Lu

https://www.biorxiv.org/content/10.1101/2024.04.11.589010v2

The mechanism of intra-Golgi secretory transport remains unclear, with the cisternal progression and stable compartment models under debate. In this study, the researchers utilize advanced Golgi imaging in nocodazole-induced ministacks, and report cargo transport velocity decreases from the cis to trans side and varies among different cargos. These findings challenge the cisternal progression model and support the stable compartment hypothesis for Golgi organization.

Picked by: Vibha Singh

Mitochondrial function regulates cell growth kinetics to actively maintain mitochondrial homeostasis

Leeba Ann Chacko, Hidenori Nakaoka, Richard Morris, Wallace Marshall, Vaishnavi Ananthanarayanan

https://www.biorxiv.org/content/10.1101/2025.03.31.646474v1

This work focuses on the scaling of mitochondria with cell size and its implications in growth and division. Using a microfluidic yeast ‘mother machine’, they tracked the growth of yeast cells and mitochondrial volume over several generations. They shed light on how mitochondrial volume dictates the time of cell division, linking cellular growth rates to the homeostasis of mitochondrial volume.

Picked by: Girish Kale

From Chacko et al. (2025). This image is made available under a CC-BY-NC-ND 4.0 International license.

Lysosome positioning affects NLRP3 inflammasome activation

Billie J. Matchett, Jack P. Green, Paula I. Seoane, Abigail Owen, Tomasz Drobkiewicz, Hayley Bennett, Antony Adamson, Gloria Lopez-Castejon, Christopher Hoyle, Martin Lowe, David Brough

https://www.biorxiv.org/content/10.1101/2025.03.21.644552v1

This preprint shows a novel link between lysosome positioning and NLRP3 inflammasome activation, indicating that positioning lysosomes at the cell periphery increases inflammasome activation in response to nigericin in macrophages. This finding suggests that the subcellular organization of lysosomes plays a role in regulating inflammatory responses.

Picked by: Felipe Del Valle Batalla

Microtubule acetylation is a biomarker of cytoplasmic health during cellular senescence

Yusheng Shen, Roilea Maxson, Richard J. McKenney, Kassandra M. Ori-McKenney

https://www.biorxiv.org/content/10.1101/2025.03.31.646469v1

This preprint interestingly demonstrates that cytosolic viscosity and microtubule dynamics influence each other. Particularly, level of microtubule acetylation affects rate of diffusion in the cytoplasm.

Picked by: Matthew Davies

Cell signalling and mechanosensing

TDP-43 directly inhibits RNA accumulation in neurites through modulation of RNA stability

Charlie Moffatt, Ankita Arora, Katherine F. Vaeth, Bryan B. Guzman, Gurprit Bhardwaj, Audrey Hoelscher, Levi B. Gifford, Holger A. Russ, Daniel Dominguez, J. Matthew Taliaferro

https://doi.org/10.1101/2025.02.25.640092

This work demonstrates that TDP-43 primarily inhibits RNA accumulation in neurites by destabilizing target RNAs, challenging our previous understanding. It also suggests that ALS-associated TDP-43 mutations disrupt this regulatory role, potentially contributing to disease.

Picked by: Felipe Del Valle Batalla

Mechanotransduction and Biophysical Regulation of Fibroblast Plasticity Under Prolonged Shear Stress

Neha Paddillaya, Anahita Jayaram, Paturu Kondaiah, Namrata Gundiah

https://www.biorxiv.org/content/10.1101/2025.03.03.641342v2

The study highlights the influence of prolonged mechanical shear on fibroblasts inducing FMT (Fibroblast-to-myofibroblast transition). The transition is not only characterized by an altered morphology, a myofibroblast-like elongated shape 12 hours post-shear but also temporally altered expression levels of vinculin and zyxin (mature focal adhesion) in those transitioned cells retaining a mechanical memory.

Picked by: Sristilekha Nath

From Paddillaya et al. (2025). This image is made available under a CC-BY 4.0 International license.

Polyploidy promotes transformation of epithelial cells into non-professional phagocytes

Yi-Chun Huang, Caique Almeida Machado Costa, Nicolas Vergara Ruiz, Xianfeng Wang, Allison Jevitt, Christina Marie Breneman, Chun Han, Wu-Min Deng

https://www.biorxiv.org/content/10.1101/2025.03.24.645044v1

This preprint draws strong correlations between polyploidy (through endoreplication) and cells taking up an additional role as phagocytes in a non-professional capacity.

Picked by: Girish Kale

Regulation of plasma membrane tension through hydrostatic pressure and actin protrusion forces

Yogishree Arabinda Panda, Elisabeth Fischer-Friedrich

https://www.biorxiv.org/content/10.1101/2025.03.24.645030v1

The plasma membrane serves as a crucial signalling hub, with its mechanical tension influencing both membrane trafficking and signalling activity. However, the mechanisms regulating membrane tension remain unclear. Findings from this study reveal that the actin cytoskeleton regulates membrane tension through two mechanisms, (1) modulating intracellular hydrostatic pressure. (2) adjusting polymerization forces in actin-rich protrusions. Furthermore, authors highlight discrepancies between bare and apparent membrane tension, demonstrating that tether forces do not reliably reflect in-plane membrane tension.

Picked by: Vibha Singh

Microtubule detyrosination alters nuclear mechanotransduction and leads to pro-hypertrophic signaling in hypertrophic cardiomyopathy

Inez Duursma, Edgar E. Nollet, Valentijn Jansen, Janaya A. Malone, Jet S. Bloem, Kenneth Bedi, Kenneth B. Margulies, Stephan A.C. Schoonvelde, Michelle Michels, Nicole N. van der Wel, Jolanda van der Velden, Tyler J. Kirby, Diederik W.D. Kuster

https://doi.org/10.1101/2025.03.28.646061

Characterizing nuclear shape abnormalities in cardiomyopathy, this study highlights a microtubule detyrosination-mediated nuclear deformation that ultimately impairs mechanotransduction.

Picked by: Sristilekha Nath

E-cadherin mechanotransduction activates EGFR-ERK signaling in epithelial cells by inducing ADAM-mediated ligand shedding

Ronja M. Houtekamer, Mirjam C. van der Net, Marjolein J. Vliem, Tomas E.J.C. Noordzij, Lisa van Uden, Robert M. van Es, Joo Yong Sim, Eriko Deguchi, Kenta Terai, Matthew A. Hopcroft, Harmjan R. Vos, Beth P. Pruitt, Michiyuki Matsuda, Willem-Jan Pannekoek, Martijn Gloerich

https://www.biorxiv.org/content/10.1101/2025.03.06.641828v1

This work is relevant because it uncovers a novel mechanism by which cells integrate mechanical and biochemical cues: mechanical strain sensed by E-cadherin triggers the ADAM-mediated release of EGFR ligands, leading to EGFR-ERK signalling.

Picked by: Felipe Del Valle Batalla

Cavin1 binding nanobodies reveal structural flexibility and regulated interactions of the N-terminal coiled-coil domain

Ya Gao, Vikas A. Tillu, Yeping Wu, James Rae, Thomas E. Hall, Kai-en Chen, Saroja Weeratunga, Qian Guo, Emma Livingstone, Wai-Hong Tham, Robert G. Parton, Brett M. Collins

https://www.biorxiv.org/content/10.1101/2024.11.26.625551v2

Caveolae are plasma membrane invaginations, composed of caveolins, cavins and lipids, which regulate membrane homeostasis, signalling, and mechanoprotection. This study identifies a nanobody targeting the HR1 domain of Cavin1, not perturbing its membrane binding, revealing a symmetric 3:3 structure and an open conformation critical for membrane interactions. A phosphomimic mutation highlights selective Cavin2/Cavin3 association, offering insights into caveolae assembly and new nanobody tools for structural & functional studies.

Picked by: Vibha Singh

Adhesion-driven tissue rigidification triggers epithelial cell polarity

Laura Rustarazo-Calvo, Cristina Pallares-Cartes, Adrián Aguirre-Tamaral, Elisa Floris, Maximilian Hingerl, Camilla Autorino, Arif Ul Maula Khan, Bernat Corominas-Murtra, Nicoletta I. Petridou

https://www.biorxiv.org/content/10.1101/2025.03.18.644006v1.full

This preprint tries to understand how tissues can transition from a fluid- to a solid-like material state. This impacts tissue organization, in terms of apico-basal cell polarity and lumen formation, and has implications for early embryo development.

Picked by: Girish Kale

PIEZO1 Drives Trophoblast Fusion and Placental Development

Yang Zhang, Ke Z. Shan, Pengfei Liang, Augustus J. Lowry, Liping Feng, Huanghe Yang

https://www.biorxiv.org/content/10.1101/2025.03.25.645313v1

The authors explore trophoblast mechanobiology during pregnancy, identifying PIEZO1 as a key regulator of trophoblast fusion- an essential mechanical adaptation for placentation.

Picked by: Sristilekha Nath

From Zhang et al. (2025). This image is made available under a CC-BY-NC-ND 4.0 International license.

Mechanical fracturing of the extracellular matrix patterns the vertebrate heart

Christopher Chan Jin Jie, Daniel Santos-Oliván, Marie-Christine Ramel, Juliana Sánchez-Posada, Toby G R Andrews, Priscilla Paizakis, Emily S Noël, Alejandro Torres-Sánchez, Rashmi Priya

https://www.biorxiv.org/content/10.1101/2025.03.07.641942v1

This work uncovers a previously unknown morphogenetic strategy where mechanical forces from heart contractions fracture the cardiac extracellular matrix (cECM), and these fractures then spatially pattern the single-cell delamination that initiates trabeculation, a process critical for heart function.

Picked by: Felipe Del Valle Batalla

Optogenetic and chemical genetic tools for rapid repositioning of vimentin intermediate filaments

Milena Pasolli, Joyce C. M. Meiring, James P. Conboy, Gijsje H. Koenderink, Anna Akhmanova

https://www.biorxiv.org/content/10.1101/2024.11.21.624725v2

This preprint establishes new tools to redistribute intermediate filaments (vimentin) by coupling them to microtubules. The tools now add precise control to the perturbations, being able to perturb the Vimentin distribution with subcellular specificity.

Picked by: Girish Kale

Genetics and genomics

Disturbed Flow Induces Reprogramming of Endothelial Cells to Immune-like and Foam Cells under Hypercholesterolemia during Atherogenesis

Christian Park, Kyung In Baek, Ruei-Chun Hung, Leandro Choi, Kiyoung Jeong, Paul Kim, Andrew Keunho Jahng, Jung Hyun Kim, Mostafa Meselhe, Ashwin Kannan, Chien-Ling Chou, Dong Won Kang, Eun Ju Song, Yerin Kim, Jay Aaron Bowman-Kirigin, Michael David Clark, Sander W. van der Laan, Gerard Pasterkamp, Nicolas Villa-Roel, Alyssa Panitch, Hanjoong Jo

https://www.biorxiv.org/content/10.1101/2025.03.06.641843v1

Through extensive transcriptomics and lineage tracing, this study demonstrates that under disrupted bloodflow and high cholesterol conditions, endothelial cells are reprogrammed to become various immune cell types, triggering plaque development. Neither disrupted bloodflow nor high cholesterol alone are sufficient to induce this reprogramming.

Picked by: Matthew Davies

Mitochondrially Transcribed dsRNA Mediates Manganese-induced Neuroinflammation

Avanti Gokhale, Hadassah Mendez-Vazquez, Maureen M. Sampson, Felix G Rivera Moctezuma, Adriana Harbuzariu, Anson Sing, Stephanie A. Zlatic, Anne M. Roberts, Milankumar Prajapati, Blaine R. Roberts, Thomas B. Bartnikas, Levi B. Wood, Steven A. Sloan, Victor Faundez, Erica Werner

https://www.biorxiv.org/content/10.1101/2025.02.16.638529v1

In this preprint, the authors could show that manganese treatment causes mitochondrial dysfunction and neuroinflammation triggered by dsRNAs derived from the mitochondria.

Picked by: Ethan Ewe

Inhibition of cytosolic DNA sensing and transposon activity safeguards pluripotency

Ferran Garcia-Llagostera, Audrey LK Putman, Alexandros Choromidis, Bryony J Leeke, Klaudia Stanik, Antonia Ramos-Guzmán, Benjamin Moyon, Jesus Gil, Alexis R. Barr, Michelle Percharde

https://www.biorxiv.org/content/10.1101/2025.03.26.645264v1

Expression of transposable elements (TEs) has numerous detrimental effects, including DNA damage and an aggressive immune response, so is actively repressed. In embryonic stem cells (ESCs), however, TE expression is loosely allowed. How then do ESCs escape the negative consequences of TE expression? In this study, the authors find multiple mechanisms that suppress the immune response following TE expression, allowing normal embryonic development.

Picked by: Matthew Davies

A natural mechanism of eukaryotic horizontal gene transfer

Andrew S. Urquhart, Samuel O’Donnell, Emile Gluck-Thaler, Aaron A. Vogan

https://www.biorxiv.org/content/10.1101/2025.02.28.640899v1

This amazing preprinted study captured active horizontal gene transfer events in the lab in eukaryotes for the first time by co-culturing different fungal species.

Picked by: Ethan Ewe

From Urquhart et al. (2025). This image is made available under a CC-BY-NC-ND 4.0 International license.

Network properties constrain natural selection on gene expression in Caenorhabditis elegans

Tyler R. Inskeep, Simon C. Groen

https://www.biorxiv.org/content/10.1101/2025.02.19.639144v1

This preprint explores how gene expression evolves in a C. elegans natural population. It turns out that genes in the germline and nervous system are under stronger selection.

Picked by: Ethan Ewe

An RNA Splicing System that Excises Transposons from Animal mRNAs

Long-Wen Zhao, Christopher Nardone, Joao A. Paulo, Stephen J. Elledge, Scott Kennedy

https://www.biorxiv.org/content/10.1101/2025.02.14.638102v1

This amazing preprint reports a novel mechanism of RNA splicing called SOS splicing that cuts transposon from mRNA!

Picked by: Ethan Ewe

Sequencing by Expansion (SBX) – a novel, high-throughput single-molecule sequencing technology

Mark Kokoris, Robert McRuer, Melud Nabavi, Aaron Jacobs, Marc Prindle, Cynthia Cech, Kendall Berg, Taylor Lehmann, Cara Machacek, John Tabone, Jagadeeswaran Chandrasekar, Lacey McGee, Matthew Lopez, Tommy Reid, Cara Williams, Salka Barrett, Alex Lehmann, Michael Kovarik, Robert Busam, Scott Miller, Brent Banasik, Brittany Kesic, Anasha Arryman, Megan Rogers-Peckham, Alan Kimura, Megan LeProwse, Mitchell Wolfin, Svetlana Kritzer, Joanne Leadbetter, Majid Babazadeh, John Chase, Greg Thiessen, William Lint, Drew Goodman, Dylan O’Connell, Nadya Lumanpauw, John Hoffman, Samantha Vellucci, Kendra Collins, Jessica Vellucci, Amy Taylor, Molly Murphy, Michael Lee, Matthew Corning

https://www.biorxiv.org/content/10.1101/2025.02.19.639056v1.full.pdf+html

This preprint is super interesting, as it’s about a breakthrough in single-molecule sequencing. The preprint authors describe key innovations to the Sequencing by Expansion (SBX) technology, allowing it to function with a single pore system, and hence drastically improve the signal-to-noise ratio usually observed in Nanopore sequencing.

Picked by: Deevitha Balasubramanian

Cap-adjacent 2’-O-ribose methylation of RNA in C. elegans is required for postembryonic growth and germline development in the presence of the decapping exonuclease EOL-1

Eileen Clemens, Sarah Brivo, Mohammed Al-Khafaji, Peter Eijlers, Maheshika Kurukulasuriya, Irmgard U. Haussmann, David MacLeod, Marius Wenzel, Berndt Müller, Matthias Soller, Jonathan Pettitt

https://www.biorxiv.org/content/10.1101/2025.03.10.638824v1

This preprint demonstrates a role for cOMe modification in regulating germline development and innate immunity in C. elegans.

Picked by: Ethan Ewe

A SET domain-containing protein and HCF-1 maintain transgenerational epigenetic memory

Chenming Zeng, Giulia Furlan, Miguel Vasconcelos Almeida, Juan C. Rueda-Silva, Jonathan Price, Jonas Mars, Pedro Rebelo-Guiomar, Meng Huang, Shouhong Guang, Falk Butter, Eric A. Miska

https://www.biorxiv.org/content/10.1101/2025.03.25.645221v1

This preprint reports a new regulator of small RNA inheritance in C. elegans. It shows how chromatin factors might regulate small RNA biogenesis

Picked by: Ethan Ewe

Epistatic impacts of cis- and trans-regulatory mutations on the distribution of mutational effects for gene expression in Saccharomyces cerevisiae

Eden McQueen, Bing Yang, Patricia J. Wittkopp

https://www.biorxiv.org/content/10.1101/2025.03.26.645465v1

This great preprint provides an explanation for the prevalence of compensatory mutations in yeast.

Picked by: Ethan Ewe

From McQueen et al. (2025). This image is made available under a CC-BY-NC-ND 4.0 International license.

Other (Biophysics & Cell cycle and division)

Remodeling of self-assembled microvascular networks under long term flow

Marie Floryan, Elena Cambria, Adriana Blazeski, Mark F. Coughlin, Zhengpeng Wan, Giovanni Offeddu, Vinayak Vinayak, Aayush Kant, Vivek Shenoy, Roger D. Kamm

https://www.biorxiv.org/content/10.1101/2025.03.17.643791v1

This study shows the full characterization of long-term 51 days of 3D perfusable vascular networks under continuous flow conditions. Continuous flow recovers perfusion of regressed vessels, and in perfusing initially healthy vessels, and can be used to study long-term diseases and to incorporate aspects of hemodynamic processes previously not captured by microphysiological systems.

Picked by: Prasanna Padmanaban

Three-dimensional cellularization in chytrid fungi uses distinct mechanisms from those driving one- and two-dimensional cytokinesis in animals and yeast

Edgar M. Medina, Mary W. Elting, Lillian Fritz-Laylin

https://www.biorxiv.org/content/10.1101/2025.01.30.635136

This preprint focuses on cellularization in Chytrid fungi. These fungi don’t proliferate through simple division. Instead, they go through nuclear division and dispersal in 3D volume, followed by cellularization that separates and creates a cell aggregate, which then disperses. The process of cellularization has similarities to cell division (1D cellularization), and cellularization in, say, Drosophila (2D cellularization), while key differences exist, which this manuscript explores.

Picked by: Girish Kale