Menu

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

Preprint posted on September 17, 2018 https://www.biorxiv.org/content/early/2018/09/17/388553

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

Posted on: 15th November 2018

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:

    Blue light induces neuronal-activity-regulated gene expression in the absence of optogenetic proteins

    Kelsey M. Tyssowski, Jesse M. Gray



    Selected by Zheng-Shan Chong

    HIV-1 Gag specifically restricts PI(4,5)P2 and cholesterol mobility in living cells creating a nanodomain platform for virus assembly

    C. Favard, J. Chojnacki, P. Merida, et al.



    Selected by Amberley Stephens

    Microfluidic protein isolation and sample preparation for high resolution cryo-EM

    Claudio Schmidli, Stefan Albiez, Luca Rima, et al.



    Selected by David Wright

    ENDOSOMAL MEMBRANE TENSION CONTROLS ESCRT-III-DEPENDENT INTRA-LUMENAL VESICLE FORMATION

    Vincent Mercier, Jorge Larios, Guillaume Molinard, et al.



    Selected by Nicola Stevenson

    1

    Planar differential growth rates determine the position of folds in complex epithelia

    Melda Tozluoğlu, Maria Duda, Natalie J Kirkland, et al.

    AND

    Buckling of epithelium growing under spherical confinement

    Anastasiya Trushko, Ilaria Di Meglio, Aziza Merzouki, et al.



    Selected by Sundar Naganathan

    2

    Microtubules stabilize intercellular contractile force transmission during tissue folding



    Selected by Ivana Viktorinová

    Dynamic Aha1 Co-Chaperone Binding to Human Hsp90

    Javier Oroz, Laura J Blair, Markus Zweckstetter



    Selected by Reid Alderson

    1

    A DNA-based voltmeter for organelles

    Anand Saminathan, John Devany, Kavya S Pillai, et al.



    Selected by Robert Mahen

    1

    Central spindle microtubules are strongly coupled to chromosomes during both anaphase A and anaphase B

    Che-Hang Yu, Stefanie Redemann, Hai-Yin Wu, et al.



    Selected by Federico Pelisch

    1

    Mechanical Stretch Kills Transformed Cancer Cells

    Ajay Tijore, Mingxi Yao, Yu-Hsiu Wang, et al.



    Selected by Joseph Jose Thottacherry

    Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells

    Quynh Nguyen, Zhen Liu, Rashmi Nanjundappa, et al.



    Selected by Robert Mahen

    Force inference predicts local and tissue-scale stress patterns in epithelia

    Weiyuan Kong, Olivier Loison, Pruthvi Chavadimane Shivakumar, et al.



    Selected by Sundar Naganathan

    Single molecule localization microscopy with autonomous feedback loops for ultrahigh precision

    Simao Coelho, Jongho Baek, Matthew S Graus, et al.



    Selected by Lars Hubatsch

    Phase transition and amyloid formation by a viral protein as an additional molecular mechanism of virus-induced cell toxicity

    Edoardo Salladini, Claire Debarnot, Vincent Delauzun, et al.



    Selected by Tessa Sinnige

    Single molecule localization microscopy with autonomous feedback loops for ultrahigh precision

    Simao Coelho, Jongho baek, Matthew S Graus, et al.



    Selected by Sam Barnett

    Applications, Promises, and Pitfalls of Deep Learning for Fluorescence Image Reconstruction

    Chinmay Belthangady , Loic A. Royer



    Selected by Romain F. Laine

    Also in the cancer biology category:

    Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues

    Adam K. Glaser, Nicholas P. Reder, Ye Chen, et al.



    Selected by Tim Fessenden

    1

    Myc instructs and maintains pancreatic adenocarcinoma phenotype

    Nicole M Sodir, Roderik M Kortlever, Valentin JA Barthet, et al.



    Selected by William Hill

    Quantification of microenvironmental metabolites in murine cancer models reveals determinants of tumor nutrient availability

    Mark R Sullivan, Laura V Danai, Caroline A Lewis, et al.



    Selected by Maria Rafaeva

    1

    Mechanical Stretch Kills Transformed Cancer Cells

    Ajay Tijore, Mingxi Yao, Yu-Hsiu Wang, et al.



    Selected by Joseph Jose Thottacherry

    Inactive USP14 and inactive UCHL5 cause accumulation of distinct ubiquitinated proteins in mammalian cells

    Jayashree Chadchankar, Victoria Korboukh, Peter Doig, et al.



    Selected by Mila Basic

    A conserved MFS orchestrates a subset of O-glycosylation to facilitate macrophage dissemination and tissue invasion

    Katarina Valoskova, Julia Biebl, Marko Roblek, et al.



    Selected by Giuliana Clemente

    1

    MRE11-RAD50-NBS1 activates Fanconi Anemia R-loop suppression at transcription-replication conflicts

    Emily Yun-Chia Chang, James P Wells, Shu-Huei Tsai, et al.



    Selected by Katie Weiner

    1

    Basal extrusion drives cell invasion and mechanical stripping of E-cadherin

    John Fadul, Gloria M Slattum, Nadja M Redd, et al.



    Selected by William Hill

    Molecularly distinct models of zebrafish Myc-induced B cell leukemia

    Chiara Borga, Clay Foster, Sowmya Iyer, et al.



    Selected by Hannah Brunsdon

    1

    The landscape of antigen-specific T cells in human cancers

    Bo Li, Longchao Liu, Jian Zhang, et al.



    Selected by Rob Hynds

    1

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

    Andrea Palamidessi, Chiara Malinverno, Emanuela FRITTOLI, et al.



    Selected by Tim Fessenden

    1

    STAT3 promotes melanoma metastasis by CEBP-induced repression of the MITF pigmentation pathway

    Alexander Swoboda, Robert Soukup, Katharina Kinslechner, et al.



    Selected by Hannah Brunsdon

    Memory sequencing reveals heritable single cell gene expression programs associated with distinct cellular behaviors

    Sydney M Shaffer, Benjamin L Emert, Ann E. Sizemore, et al.



    Selected by Leighton Daigh

    2

    Anti-angiogenic effects of VEGF stimulation on endothelium deficient in phosphoinositide recycling

    Amber N Stratman, Olivia M Farrelly, Constantinos M Mikelis, et al.



    Selected by Coert Margadant

    Profiling the surface proteome identifies actionable biology for TSC1 mutant cells beyond mTORC1 signaling

    Junnian Wei, Kevin K. Leung, Charles Truillet, et al.



    Selected by Rob Hynds

    1

    Precise tuning of gene expression output levels in mammalian cells

    Yale S. Michaels, Mike B Barnkob, Hector Barbosa, et al.



    Selected by Tim Fessenden

    1

    Also in the cell biology category:

    Blue light induces neuronal-activity-regulated gene expression in the absence of optogenetic proteins

    Kelsey M. Tyssowski, Jesse M. Gray



    Selected by Zheng-Shan Chong

    Mutations in the Insulator Protein Suppressor of Hairy Wing Induce Genome Instability

    Shih-Jui Hsu, Emily C. Stow, James R. Simmons, et al.



    Selected by Maiko Kitaoka

    1

    Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues

    Adam K. Glaser, Nicholas P. Reder, Ye Chen, et al.



    Selected by Tim Fessenden

    1

    ATAT1-enriched vesicles promote microtubule acetylation via axonal transport

    Aviel Even, Giovanni Morelli, Chiara Scaramuzzino, et al.



    Selected by Stephen Royle

    1

    HIV-1 Gag specifically restricts PI(4,5)P2 and cholesterol mobility in living cells creating a nanodomain platform for virus assembly

    C. Favard, J. Chojnacki, P. Merida, et al.



    Selected by Amberley Stephens

    Hepatocyte-specific deletion of Pparα promotes NASH in the context of obesity

    Marion Regnier, Arnaud Polizzi, Sarra Smati, et al.



    Selected by Pablo Ranea Robles

    Mitochondrial biogenesis is transcriptionally repressed in lysosomal lipid storage diseases

    King Faisal Yambire, Lorena Fernandez-Mosquera, Robert Steinfeld, et al.



    Selected by Sandra Franco Iborra

    1

    Thyroid hormone regulates distinct paths to maturation in pigment cell lineages

    Lauren Saunders, Abhishek Mishra, Andrew J Aman, et al.



    Selected by Hannah Brunsdon

    1

    Kinesin-6 Klp9 plays motor-dependent and -independent roles in collaboration with Kinesin-5 Cut7 and the microtubule crosslinker Ase1 in fission yeast

    Masashi Yukawa, Masaki Okazaki, Yasuhiro Teratani, et al.



    Selected by I. Bouhlel

    A pair of E3 ubiquitin ligases compete to regulate filopodial dynamics and axon guidance

    Nicholas P Boyer, Laura E McCormick, Fabio L Urbina, et al.



    Selected by Angika Basant

    1

    SorCS1-mediated Sorting of Neurexin in Dendrites Maintains Presynaptic Function

    Luis Filipe Ribeiro, Ben Verpoort, Julie Nys, et al.



    Selected by Carmen Adriaens

    1

    ENDOSOMAL MEMBRANE TENSION CONTROLS ESCRT-III-DEPENDENT INTRA-LUMENAL VESICLE FORMATION

    Vincent Mercier, Jorge Larios, Guillaume Molinard, et al.



    Selected by Nicola Stevenson

    1

    Microtubules stabilize intercellular contractile force transmission during tissue folding



    Selected by Ivana Viktorinová

    Synthetic pluripotent bacterial stem cells

    Sara Molinari, David L. Shis, James Chappell, et al.



    Selected by Lorenzo Lafranchi

    A DNA-based voltmeter for organelles

    Anand Saminathan, John Devany, Kavya S Pillai, et al.



    Selected by Robert Mahen

    1

    Central spindle microtubules are strongly coupled to chromosomes during both anaphase A and anaphase B

    Che-Hang Yu, Stefanie Redemann, Hai-Yin Wu, et al.



    Selected by Federico Pelisch

    1

    Close