Close

Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma.

Andrea Palamidessi, Chiara Malinverno, Emanuela FRITTOLI, Salvatore Corallino, Elisa Barbieri, Sara Sigismund, Pier Paolo Di Fiore, Galina V Beznoussenko, Emanuele Martini, Massimiliano Garrè, Dario Parazzoli, Ines Ferrara, Claudio Tripodo, Fabio Giavazzi, Roberto Cerbino, Giorgio Scita

Posted on: 15 November 2018

Preprint posted on 17 September 2018

Article now published in Nature Materials at http://dx.doi.org/10.1038/s41563-019-0425-1

Endocytic growth factor signaling induces proliferation and solid-to-liquid transitions in confluent epithelial tissues in 2D and 3D cell culture.

Selected by Tim Fessenden

Context

Granular materials (think of sand or grains of rice) can transition between a flowing, liquid-like state to a jammed state upon application or removal of an external stress. In the jammed state, constituent particles can no longer rearrange and the material behaves like a solid. While we find this a rather intuitive property of granular materials, a growing literature has proposed and characterized jamming and unjamming transitions in biological tissues.

Both mathematical models and experimental observations have built a strong case that tissues can exhibit liquid-like behaviors, such as cell rearrangements, or solid-like behaviors such as resistance to tension or compression1. Monolayers of epithelial cells can interchange between such states, driven for instance by changes in cell contractility or cell-cell adhesions2. Jamming thus offers a simple yet formalized physical framework to describe the material properties of tissues as an emergent property of actomyosin cytoskeletal dynamics. However, this framework is still poorly integrated with established biochemical signaling and cell motility behaviors in 2D and 3D culture.

Data

The present work offers a thorough analysis of the unjamming transition, including growth factor signaling, single-cell behaviors, and motility in 2D and 3D culture using MCF-10A, a human mammary epithelial cell line. Palamidessi and colleagues observe that within confluent monolayers, MCF-10A cells are normally immobile, corresponding to a jammed state, but become unjammed upon inducible expression of the endocytic receptor RAB5A. Previous work from this group showed potent effects of RAB5A on cell motility and invasion3. In more recent work, RAB5A was implicated in actomyosin dynamics driving unjamming in epithelial monolayers4. Here the authors use a suite of methods to demonstrate that RAB5A directly tunes growth factor signaling in endosomes, which leads to unjamming in MCF-10A monolayers through the actin regulator Wave-2.

Previous work analyzing jamming/unjamming transitions has relied on monolayers in 2D culture, where cells are immobile within jammed tissues. How are these behaviors manifested in spherical organoids? Curiously, inducible expression of RAB5A in mature organoids grown in Matrigel drives local rearrangement of neighboring cells, but in a context of rapid organoid rotation. Rotation has no immediate correlate for 2D monolayers but has been often observed in organoids, raising questions about the origin and significance of organoid rotation. When organoids were grown in collagen/matrigel mixtures, RAB5A expression induced multicellular invasion or budding into the matrix. Presumably this followed from rotation and rearrangements as observed in matrigel, in agreement with this reader’s published observations5. The authors conclude that RAB5A can induce first unjamming and invasion of initially immobile tissues, linking unjamming directly with phenotypes of malignant tissues in 2D and 3D.

Implications

By exploring this “reawakening” of cell motility in confluent tissues, Palamidessi and colleagues tie the perhaps overly broad phenomenon of unjamming to a set of well-studied motility and proliferative cell behaviors. This work invites the reader to rethink what cell motility means for epithelia and, just as important, provides an excellent example of how to study cell motility in both 2D and 3D contexts within one body of work.

Cell movements within control or RAB5A-expressing epithelial spheroids. Yellow arrows indicate movements of nuclei. Red arrow indicates the axis of rotation for each example. Plots at right indicate the time evolution of the velocity (top) and the rotational order parameter (bottom). Reproduced with permission from Figure 6B.

 

References

  1. Mongera, A. et al. A fluid-to-solid jamming transition underlies vertebrate body axis elongation. Nature 561, 401–405 (2018).
  2. Bi, D., Lopez, J. H., Schwarz, J. M. & Manning, M. L. A density-independent rigidity transition in biological tissues. Nat. Phys. 11, 1074–1079 (2015).
  3. Frittoli, E. et al. A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination. J. Cell Biol. 206, 307–328 (2014).
  4. Malinverno, C. et al. Endocytic reawakening of motility in jammed epithelia. Nat. Mater. 16, 587–596 (2017).
  5. Fessenden, T. B. et al. Dia1-dependent adhesions are required by epithelial tissues to initiate invasion. J. Cell Biol. 217, 1485–1502 (2018).

Tags: 3d, invasion, mcf-10a, motility, unjamming

doi: https://doi.org/10.1242/prelights.5571

Read preprint (No Ratings Yet)

Author's response

Giorgio Scita shared

Question:

Coherent angular rotation does not necessarily require unjamming, if we define unjamming as the ability to undergo neighbor exchange. Do you interpret those results as motility of a jammed tissue?

Author response:

I totally agree that circular angular rotation does not require unjamming, we have one set of measurements, however, where we looked at the overlap parameter Q […] Q is a function of time that decays from 1 to 0 according to the number of nuclei that have been substantially displaced from their original position, when observed in a reference frame co-moving with the whole spheroid. In RAB5A spheroids we observe a significantly faster decay indicative of local cell rearrangement (i.e. liquid motion). Thus we believe, that like in 2D monolayers, what RAB5A does is to cause long range correlated motion in the presence of local unjamming.

Have your say

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

Also in the biophysics category:

Engineered Nanotopographies Induce Transient Openings in the Nuclear Membrane

Einollah Sarikhani, Vrund Patel, Zhi Li, et al.

Selected by 23 September 2024

Sristilekha Nath

Bioengineering

Spiral-eyes: A soft active matter model of in vivo corneal epithelial cell migration

Kaja Kostanjevec, Rastko Sknepnek, Jon Martin Collinson, et al.

Selected by 03 September 2024

Prasanna Padmanaban

Biophysics

The actin cortex acts as a mechanical memory of morphology in confined migrating cells

Yohalie Kalukula, Marine Luciano, Guillaume Charras, et al.

Selected by 20 August 2024

Prasanna Padmanaban, Vibha SINGH

Biophysics

Also in the cancer biology category:

Integrin conformation-dependent neutrophil slowing obstructs the capillaries of the pre-metastatic lung in a model of breast cancer

Frédéric Fercoq, Gemma S. Cairns, Marco De Donatis, et al.

Selected by 07 October 2024

Simon Cleary

Cancer Biology

Mitochondria-derived nuclear ATP surge protects against confinement-induced proliferation defects

Ritobrata Ghose, Fabio Pezzano, Savvas Kourtis, et al.

Selected by 16 May 2024

Teodora Piskova

Cell Biology

Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis thymoma

Yoshiaki Yasumizu, Makoto Kinoshita, Martin Jinye Zhang, et al.

Selected by 27 March 2024

Jessica Chevallier

Immunology

Also in the cell biology category:

The RNA binding protein HNRNPA2B1 regulates RNA abundance and motor protein activity in neurites

Joelle Lo, Katherine F. Vaeth, Gurprit Bhardwaj, et al.

Selected by 24 September 2024

Felipe Del Valle Batalla

Neuroscience

Pharyngeal neuronal mechanisms governing sour taste perception in Drosophila melanogaster

Bhanu Shrestha, Jiun Sang, Suman Rimal, et al.

Selected by 23 September 2024

Matthew Davies

Cell Biology

Feedback regulation by the RhoA-specific GEF ARHGEF17 regulates actomyosin network disassembly

Vasundhara Rao, Benjamin Grädel, Lucien Hinderling, et al.

Selected by 18 September 2024

Vibha SINGH

Cell Biology

Also in the cancer biology category:

BSCB-Biochemical Society 2024 Cell Migration meeting

This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.

 



List by Reinier Prosee

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.

 



List by Nadja Hümpfer et al.

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

Single Cell Biology 2020

A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.

 



List by Alex Eve

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Anticancer agents: Discovery and clinical use

Preprints that describe the discovery of anticancer agents and their clinical use. Includes both small molecules and macromolecules like biologics.

 



List by Zhang-He Goh

Also in the cell biology category:

BSCB-Biochemical Society 2024 Cell Migration meeting

This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.

 



List by Reinier Prosee

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

The Society for Developmental Biology 82nd Annual Meeting

This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.

 



List by Joyce Yu, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.

 



List by Nadja Hümpfer et al.

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.

 



List by Alex Eve

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

BioMalPar XVI: Biology and Pathology of the Malaria Parasite

[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria

 



List by Dey Lab, Samantha Seah

1

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.

 



List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.

 



List by Paul Gerald L. Sanchez and Stefano Vianello

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome

 



List by Hiral Shah

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Dey Lab

Autophagy

Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.

 



List by Sandra Malmgren Hill

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Cellular metabolism

A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.

 



List by Pablo Ranea Robles

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019

 



List by Dey Lab

MitoList

This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.

 



List by Sandra Franco Iborra

Biophysical Society Annual Meeting 2019

Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA

 



List by Joseph Jose Thottacherry

ASCB/EMBO Annual Meeting 2018

This list relates to preprints that were discussed at the recent ASCB conference.

 



List by Dey Lab, Amanda Haage
Close