Close

“Viscotaxis”- Directed Migration of Mesenchymal Stem Cells in Response to Loss Modulus Gradient

Pallavi Uday Shirke, Hiya Goswami, Vardhman Kumar, Darshan Shah, Siddhartha Das, Jayesh Bellare, K.V. Venkatesh, Jyoti R. Seth, Abhijit Majumder

Posted on: 1 December 2020

Preprint posted on 14 October 2019

Article now published in Acta Biomaterialia at http://dx.doi.org/10.1016/j.actbio.2021.08.039

Understanding cell motility: viscotaxis

Selected by Mariana De Niz

Categories: biophysics, cell biology

Background

Directed cell migration in response to various types of gradients plays a crucial role in physiological and pathological conditions. Depending on the cue that is responsible for directed migration, several different types of “taxis” have been reported in the literature such as chemotaxis (i.e. movement in response to a chemical stimulus), haptotaxis (i.e. movement in response to adhesive substrates), rheotaxis (i.e. movement in response to currents), curvotaxis (i.e. movement in response to cell scale curvature variations), topotaxis (i.e. movement in response to signaling pathways activated by the extracellular matrix, and the control of cell stiffness), and mechanotaxis (i.e. movement in response to mechanical cues). A mechanical cue known to influence cell migration is the gradient of substrate elastic modulus. However, the elastic modulus alone cannot fully define the material properties of the cellular microenvironment, as thisoften has both elastic and viscous characteristics. While the reported literature discusses the effect of uniform viscoelasticity on cell migration, the in vivo microenvironment is rarely uniform. In their work, Shirke et al investigated the influence of viscous nature (loss modulus, G’’) on cell migration, and defined a newly reported form of cellular migration known as Viscotaxis.

Figure 1. Viscotaxis: cell migrates from High Loss to Low Loss modulus region. (From ref. 1).

Key findings and developments

            The authors began by finding acrylamide and bis-acrylamide concentrations that could give rise to polyacrylamide gels with similar storage modulus (a measure of the elastic response of the material), but different loss moduli (measure of the viscous response of the material). Following multiple characterizations, they selected two compositions that give rise to gels with the same storage modulus but widely different loss moduli- which they termed High Loss (for high loss modulus), and Low Loss (for low loss modulus). They then prepared a gel with a gradient of loss modulus using two drop technique, based on diffusion and polymerization, which allowed rheological characterization by quantifying and visualizing the gradient strength.

            Following the generation of the suitable substrates, the authors went on to explore whether the gradient of loss modulus induces directed cell migration. For this, they recorded the movement of human mesenchymal stem cells on substrates with loss modulus gradient, using time-lapse microscopy. Using this method, they reported movement of the majority of cells from High Loss to Low Loss- namely, viscotaxis. This type of migration was not observed on gels with uniform loss modulus, rather than one having a gradient. Further quantification of the tactic index confirmed that over 70% of cells respond to the modulus gradient, while 30% remain unresponsive even across time. To estimate the strength of the migration bias, the authors calculated the average cell displacement over time, and found that biased migration took about 6h to get established. Moreover, they found that more randomness in cell migration exists in Low Loss as compared to that on High Loss. Attempting to further characterize the reason for unresponsiveness on 30% of cells, the authors explored whether the initial location of a cell on a gradient determines its decision, and found this is not the case, altogether suggesting that there is a sub-population of cells that are non-responsive to a given gradient strength.

            The authors then investigated the influence of the strength of loss modulus gradient on migration bias. They generated a gel with a step increase in loss modulus and determined 4 possible cell trajectories, grouped into two types of responses- the first, positive response (following the viscotaxis gradient) involved a) cells starting in the High Loss modulus region, and crossing the boundary into the Low Loss modulus region and b) cells starting in the Low Loss modulus region and moving towards the High Loss modulus region, but instead taking a U-turn. A positive response was observed in 83% of cells. The second set of trajectories involve a negative response (contradicting the predicted viscotaxis gradient), namely a) cells crossing from the Low Loss to the High Loss modulus region, and b) cells starting in the High Loss modulus region, approaching the boundary of the Low Loss modulus region, and taking a U-turn at the boundary. Atomic force microscopy showed there was no gradient in the elastic modulus.

            Finally, the authors went on to investigate the mechanisms of viscotaxis. For this, they measured cellular traction on uniform Low Loss and High Loss substrates using traction force microscopy. They found that cells apply higher traction force on more elastic materials (i.e. materials with low loss modulus), which might result in force asymmetry, and biased displacement of cells causing viscotaxis. Upon chemical disruption of actomyosin contractility, directional migration was lost. Moreover, using HeLa cells, the authors showed that cells can maintain a stable morphology on High and Low Loss substrates, but that due to the inability to build up traction, in High Loss substrates the cell boundaries fluctuate more.

 

What I like about this preprint

             I like the interdisciplinarity of the work. Moreover I think we still know very little about all the biophysical aspects mediating cell migration. The authors conclude their preprint stating that this is one more aspect to consider when considering tissue bioengineering. I think the more we understand these biophysical aspects, the closer we will be to reproducing important aspects in vitro in increased efforts to replace in vivo models.

Open questions

  1. Have you explored the role of viscotaxis in an integrated approach as would be observed in vivo– namely, including chemotactic, durotactic, etc. gradients? What would be the main differences you would expect, in an integrated approach?
  1. What would be the role of viscotaxis under flow conditions – for instance if this were to play a role in circulating cells within the vasculature?
  1. You used two different cells types for different purposes in this study. Would you expect different behaviours with respect to viscotaxis across multiple different cells which would be representatives of various cells in the body? Would you expect something very different to what you observed in mesenchymal stem cells?
  1. One important aspect you discuss in your paper is the relevance of this finding for preparing stiffness-based substrates for the field of tissue engineering. As organs-on-chip and organoids gain momentum, how do you envisage integrating knowledge on the biophysical properties of substrates with in vivo and in vitro studies?

References

  1. Shirke PU et al, “Viscotaxis”-directed migration of mesenchymal stem cells in response to loss modulus gradient, bioRxiv, 2020.

 

doi: https://doi.org/10.1242/prelights.26007

Read preprint (No Ratings Yet)

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:

Motor Clustering Enhances Kinesin-driven Vesicle Transport

Rui Jiang, Qingzhou Feng, Daguan Nong, et al.

Selected by 16 November 2024

Sharvari Pitke

Biophysics

Global coordination of protrusive forces in migrating immune cells

Patricia Reis-Rodrigues, Nikola Canigova, Mario J. Avellaneda, et al.

Selected by 10 October 2024

yohalie kalukula

Biophysics

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

Also in the cell biology category:

Germplasm stability in zebrafish requires maternal Tdrd6a and Tdrd6c

Alessandro Consorte, Yasmin El Sherif, Fridolin Kielisch, et al.

Selected by 13 December 2024

Justin Gutkowski

Developmental Biology

Leukocytes use endothelial membrane tunnels to extravasate the vasculature

Werner J. van der Meer, Abraham C.I. van Steen, Eike Mahlandt, et al.

Selected by 08 December 2024

Felipe Del Valle Batalla

Cell Biology

Platelet-derived LPA16:0 inhibits adult neurogenesis and stress resilience in anxiety disorder

Thomas Larrieu, Charline Carron, Fabio Grieco, et al.

Selected by 04 December 2024

Harvey Roweth

Neuroscience

Also in the cell biology category:

November in preprints – the CellBio edition

This is the first community-driven preList! A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. Categories include: 1) cancer cell biology 2) cell cycle and division 3) cell migration and cytoskeleton 4) cell organelles and organisation 5) cell signalling and mechanosensing 6) genetics/gene expression

 



List by Felipe Del Valle Batalla et al.

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

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