scholarly journals A least microenvironmental uncertainty principle (LEUP) as a generative model of collective cell migration mechanisms

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Arnab Barua ◽  
Josue M. Nava-Sedeño ◽  
Michael Meyer-Hermann ◽  
Haralampos Hatzikirou
Keyword(s):  
Cell Migration ◽  
Uncertainty Principle ◽  
Collective Behavior ◽  
Statistical Physics ◽  
Cell Movement ◽  
Generative Model ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Vicsek Model ◽  
Special Case

AbstractCollective migration is commonly observed in groups of migrating cells, in the form of swarms or aggregates. Mechanistic models have proven very useful in understanding collective cell migration. Such models, either explicitly consider the forces involved in the interaction and movement of individuals or phenomenologically define rules which mimic the observed behavior of cells. However, mechanisms leading to collective migration are varied and specific to the type of cells involved. Additionally, the precise and complete dynamics of many important chemomechanical factors influencing cell movement, from signalling pathways to substrate sensing, are typically either too complex or largely unknown. The question is how to make quantitative/qualitative predictions of collective behavior without exact mechanistic knowledge. Here we propose the least microenvironmental uncertainty principle (LEUP) that may serve as a generative model of collective migration without precise incorporation of full mechanistic details. Using statistical physics tools, we show that the famous Vicsek model is a special case of LEUP. Finally, to test the biological applicability of our theory, we apply LEUP to construct a model of the collective behavior of spherical Serratia marcescens bacteria, where the underlying migration mechanisms remain elusive.

scholarly journals A least microenvironmental uncertainty principle (LEUP) as a generative model of collective cell migration mechanisms

2018 ◽  
Author(s):  
Arnab Barua ◽  
Josue M. Nava-Sedeño ◽  
Haralampos Hatzikirou
Keyword(s):  
Cell Migration ◽  
Uncertainty Principle ◽  
Collective Behavior ◽  
Cell Movement ◽  
Generative Model ◽  
Collective Cell Migration ◽  
Proof Of Concept ◽  
Collective Migration ◽  
Vicsek Model ◽  
Special Case

AbstractCollective migration is commonly observed in groups of migrating cells, in the form of swarms or aggregates. Mechanistic models have proven very useful in understanding collective cell migration. Such models, either explicitly consider the forces involved in the interaction and movement of individuals or phenomenologically define rules which mimic the observed behavior of cells. However, mechanisms leading to collective migration are varied and specific to the type of cells involved. Additionally, the precise and complete dynamics of many important chemomechanical factors influencing cell movement, from signalling pathways to substrate sensing, are typically either too complex or largely unknown. The question is how to make quantitative/qualitative predictions of collective behavior without exact mechanistic knowledge. Here we propose the least microenvironmental uncertainty principle (LEUP) that serves as a generative model of collective migration without incorporation of full mechanistic details. Interestingly we show that the famous Vicsek model is a special case of LEUP. Finally, as a proof of concept, we apply the LEUP to quantitatively study ofthe collective behavior of spherical Serratia marcescens bacteria, where the underlying migration mechanisms remain elusive.

scholarly journals Contact inhibition of locomotion probabilities drive solitary versus collective cell migration

2013 ◽  
Vol 10 (88) ◽  
pp. 20130717 ◽  
Author(s):  
Ravi A. Desai ◽  
Smitha B. Gopal ◽  
Sophia Chen ◽  
Christopher S. Chen
Keyword(s):  
Cell Migration ◽  
State Transition ◽  
Single Cells ◽  
Cell Movement ◽  
Contact Inhibition ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Agent Based ◽  
Solitary Cell

Contact inhibition of locomotion (CIL) is the process whereby cells collide, cease migrating in the direction of the collision, and repolarize their migration machinery away from the collision. Quantitative analysis of CIL has remained elusive because cell-to-cell collisions are infrequent in traditional cell culture. Moreover, whereas CIL predicts mutual cell repulsion and ‘scattering’ of cells, the same cells in vivo are observed to undergo CIL at some developmental times and collective cell migration at others. It remains unclear whether CIL is simply absent during collective cell migration, or if the two processes coexist and are perhaps even related. Here, we used micropatterned stripes of extracellular matrix to restrict cell migration to linear paths such that cells polarized in one of two directions and collisions between cells occurred frequently and consistently, permitting quantitative and unbiased analysis of CIL. Observing repolarization events in different contexts, including head-to-head collision, head-to-tail collision, collision with an inert barrier, or no collision, and describing polarization as a two-state transition indicated that CIL occurs probabilistically, and most strongly upon head-to-head collisions. In addition to strong CIL, we also observed ‘trains’ of cells moving collectively with high persistence that appeared to emerge from single cells. To reconcile these seemingly conflicting observations of CIL and collective cell migration, we constructed an agent-based model to simulate our experiments. Our model quantitatively predicted the emergence of collective migration, and demonstrated the sensitivity of such emergence to the probability of CIL. Thus CIL and collective migration can coexist, and in fact a shift in CIL probabilities may underlie transitions between solitary cell migration and collective cell migration. Taken together, our data demonstrate the emergence of persistently polarized, collective cell movement arising from CIL between colliding cells.

scholarly journals Distinct roles of tumor associated mutations in collective cell migration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rachel M. Lee ◽  
Michele I. Vitolo ◽  
Wolfgang Losert ◽  
Stuart S. Martin
Keyword(s):  
Collective Behavior ◽  
Metastatic Potential ◽  
Breast Epithelial Cell ◽  
Collective Cell Migration ◽  
Label Free ◽  
Collective Migration ◽  
Contrast Imaging ◽  
Pten Deletion

AbstractRecent evidence suggests that groups of cells are more likely to form clinically dangerous metastatic tumors, emphasizing the importance of understanding mechanisms underlying collective behavior. The emergent collective behavior of migrating cell sheets in vitro has been shown to be disrupted in tumorigenic cells but the connection between this behavior and in vivo tumorigenicity remains unclear. We use particle image velocimetry to measure a multidimensional migration phenotype for genetically defined human breast epithelial cell lines that range in their in vivo behavior from non-tumorigenic to aggressively metastatic. By using cells with controlled mutations, we show that PTEN deletion enhances collective migration, while Ras activation suppresses it, even when combined with PTEN deletion. These opposing effects on collective migration of two mutations that are frequently found in patient tumors could be exploited in the development of novel treatments for metastatic disease. Our methods are based on label-free phase contrast imaging, and thus could easily be applied to patient tumor cells. The short time scales of our approach do not require potentially selective growth, and thus in combination with label-free imaging would allow multidimensional collective migration phenotypes to be utilized in clinical assessments of metastatic potential.

scholarly journals Self-organized cell migration across scales – from single cell movement to tissue formation

Development ◽  
2021 ◽  
Vol 148 (7) ◽  
pp. dev191767
Author(s):  
Jessica Stock ◽  
Andrea Pauli
Keyword(s):  
Cell Migration ◽  
Multiple Scales ◽  
Single Cells ◽  
Cell Movement ◽  
Biological Response ◽  
Collective Cell Migration ◽  
Theoretical Concepts ◽  
Self Organizing

ABSTRACTSelf-organization is a key feature of many biological and developmental processes, including cell migration. Although cell migration has traditionally been viewed as a biological response to extrinsic signals, advances within the past two decades have highlighted the importance of intrinsic self-organizing properties to direct cell migration on multiple scales. In this Review, we will explore self-organizing mechanisms that lay the foundation for both single and collective cell migration. Based on in vitro and in vivo examples, we will discuss theoretical concepts that underlie the persistent migration of single cells in the absence of directional guidance cues, and the formation of an autonomous cell collective that drives coordinated migration. Finally, we highlight the general implications of self-organizing principles guiding cell migration for biological and medical research.

scholarly journals Polar pattern formation induced by contact following locomotion in a multicellular system

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Masayuki Hayakawa ◽  
Tetsuya Hiraiwa ◽  
Yuko Wada ◽  
Hidekazu Kuwayama ◽  
Tatsuo Shibata
Keyword(s):  
Cell Migration ◽  
Collective Behavior ◽  
Cell Interaction ◽  
Theoretical Description ◽  
Chemotactic Activity ◽  
Dictyostelium Cell ◽  
Collective Cell Migration ◽  
Contact Site ◽  
Polar Order ◽  
Cell Cell

Biophysical mechanisms underlying collective cell migration of eukaryotic cells have been studied extensively in recent years. One mechanism that induces cells to correlate their motions is contact inhibition of locomotion, by which cells migrating away from the contact site. Here, we report that tail-following behavior at the contact site, termed contact following locomotion (CFL), can induce a non-trivial collective behavior in migrating cells. We show the emergence of a traveling band showing polar order in a mutant Dictyostelium cell that lacks chemotactic activity. We find that CFL is the cell–cell interaction underlying this phenomenon, enabling a theoretical description of how this traveling band forms. We further show that the polar order phase consists of subpopulations that exhibit characteristic transversal motions with respect to the direction of band propagation. These findings describe a novel mechanism of collective cell migration involving cell–cell interactions capable of inducing traveling band with polar order.

scholarly journals Tissue self-organization based on collective cell migration by contact activation of locomotion and chemotaxis

2019 ◽  
Vol 116 (10) ◽  
pp. 4291-4296 ◽  
Author(s):  
Taihei Fujimori ◽  
Akihiko Nakajima ◽  
Nao Shimada ◽  
Satoshi Sawai
Keyword(s):  
Cell Migration ◽  
Cell Movement ◽  
Tissue Level ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Contact Activation ◽  
Membrane Recruitment ◽  
Cell Rearrangement ◽  
Cell Protrusion ◽  
Cell Cell

Despite their central role in multicellular organization, navigation rules that dictate cell rearrangement remain largely undefined. Contact between neighboring cells and diffusive attractant molecules are two of the major determinants of tissue-level patterning; however, in most cases, molecular and developmental complexity hinders one from decoding the exact governing rules of individual cell movement. A primordial example of tissue patterning by cell rearrangement is found in the social amoebaDictyostelium discoideumwhere the organizing center or the “tip” self-organizes as a result of sorting of differentiating prestalk and prespore cells. By employing microfluidics and microsphere-based manipulation of navigational cues at the single-cell level, here we uncovered a previously overlooked mode ofDictyosteliumcell migration that is strictly directed by cell–cell contact. The cell–cell contact signal is mediated by E-set Ig-like domain-containing heterophilic adhesion molecules TgrB1/TgrC1 that act in trans to induce plasma membrane recruitment of the SCAR complex and formation of dendritic actin networks, and the resulting cell protrusion competes with those induced by chemoattractant cAMP. Furthermore, we demonstrate that both prestalk and prespore cells can protrude toward the contact signal as well as to chemotax toward cAMP; however, when given both signals, prestalk cells orient toward the chemoattractant, whereas prespore cells choose the contact signal. These data suggest a model of cell sorting by competing juxtacrine and diffusive cues, each with potential to drive its own mode of collective cell migration.

scholarly journals Collective cell migration in development

2016 ◽  
Vol 212 (2) ◽  
pp. 143-155 ◽  
Author(s):  
Elena Scarpa ◽  
Roberto Mayor
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Collective Cell Migration ◽  
Germ Layer ◽  
Collective Migration ◽  
Developmental Models ◽  
Border Cell ◽  
Guidance Cues ◽  
Tracheal Branching

During embryonic development, tissues undergo major rearrangements that lead to germ layer positioning, patterning, and organ morphogenesis. Often these morphogenetic movements are accomplished by the coordinated and cooperative migration of the constituent cells, referred to as collective cell migration. The molecular and biomechanical mechanisms underlying collective migration of developing tissues have been investigated in a variety of models, including border cell migration, tracheal branching, blood vessel sprouting, and the migration of the lateral line primordium, neural crest cells, or head mesendoderm. Here we review recent advances in understanding collective migration in these developmental models, focusing on the interaction between cells and guidance cues presented by the microenvironment and on the role of cell–cell adhesion in mechanical and behavioral coupling of cells within the collective.

scholarly journals An Integrative and Modular Framework to Recapitulate Emergent Behavior in Cell Migration

2020 ◽  
Vol 8 ◽  
Author(s):  
Marina B. Cuenca ◽  
Lucía Canedo ◽  
Carolina Perez-Castro ◽  
Hernan E. Grecco
Keyword(s):  
Cell Migration ◽  
Single Cell ◽  
Cancer Progression ◽  
Collective Behavior ◽  
Cell Movement ◽  
Primary Brain Tumor ◽  
Emergent Behavior ◽  
Integrative Model ◽  
Broad Variety ◽  
Modular Framework

Cell migration has been a subject of study in a broad variety of biological systems, from morphogenetic events during development to cancer progression. In this work, we describe single-cell movement in a modular framework from which we simulate the collective behavior of glioblastoma cells, the most prevalent and malignant primary brain tumor. We used the U87 cell line, which can be grown as a monolayer or spatially closely packed and organized in 3D structures called spheroids. Our integrative model considers the most relevant mechanisms involved in cell migration: chemotaxis of attractant factor, mechanical interactions and random movement. The effect of each mechanism is integrated into the overall probability of the cells to move in a particular direction, in an automaton-like approach. Our simulations fit and reproduced the emergent behavior of the spheroids in a set of migration assays where single-cell trajectories were tracked. We also predicted the effect of migration inhibition on the colonies from simple experimental characterization of single treated cell tracks. The development of tools that allow complementing molecular knowledge in migratory cell behavior is relevant for understanding essential cellular processes, both physiological (such as organ formation, tissue regeneration among others) and pathological perspectives. Overall, this is a versatile tool that has been proven to predict individual and collective behavior in U87 cells, but that can be applied to a broad variety of scenarios.

scholarly journals Hypoxia, Partial EMT and Collective Migration: Emerging Culprits in Metastasis

2020 ◽  
Author(s):  
Kritika Saxena ◽  
Mohit Kumar Jolly ◽  
Kuppusamy Balamurugan
Keyword(s):  
Drug Resistance ◽  
Cell Migration ◽  
Epithelial Mesenchymal Transition ◽  
Biological Process ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Mesenchymal Transition ◽  
Cancer Aggressiveness ◽  
Migration Of Cells ◽  
Successful Colonization

Epithelial-mesenchymal transition (EMT) is a cellular biological process involved in migration of primary cancer cells to secondary sites facilitating metastasis. Besides, EMT also confers properties such as stemness, drug resistance and immune evasion which can aid a successful colonization at the distant site. EMT is not a binary process; recent evidence suggests that cells in partial EMT or hybrid E/M phenotype(s) can have enhanced stemness and drug resistance as compared to those undergoing a complete EMT. Moreover, partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E/M phenotypes may be the ‘fittest’ for metastasis. Here, we review mechanisms and implications of hybrid E/M phenotypes, including their reported association with hypoxia. Hypoxia-driven activation of HIF-1α can drive EMT. In addition, cyclic hypoxia, as compared to acute or chronic hypoxia, shows the highest levels of active HIF-1α and can augment cancer aggressiveness to a greater extent, including enriching for a partial EMT phenotype. We also discuss how metastasis is influenced by hypoxia, partial EMT and collective cell migration, and call for a better understanding of interconnections among these mechanisms. We discuss the known regulators of hypoxia, hybrid EMT and collective cell migration and highlight the gaps which needs to be filled for connecting these three axes which will increase our understanding of dynamics of metastasis and help control it more effectively.

scholarly journals Expression of E-Cadherin in Epithelial Cancer Cells Increases Cell Motility and Directionality through the Localization of ZO-1 during Collective Cell Migration

2021 ◽  
Vol 8 (5) ◽  
pp. 65
Author(s):  
Song-Yi Park ◽  
Hwanseok Jang ◽  
Seon-Young Kim ◽  
Dasarang Kim ◽  
Yongdoo Park ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Collective cell migration of epithelial tumor cells is one of the important factors for elucidating cancer metastasis and developing novel drugs for cancer treatment. Especially, new roles of E-cadherin in cancer migration and metastasis, beyond the epithelial–mesenchymal transition, have recently been unveiled. Here, we quantitatively examined cell motility using micropatterned free edge migration model with E-cadherin re-expressing EC96 cells derived from adenocarcinoma gastric (AGS) cell line. EC96 cells showed increased migration features such as the expansion of cell islands and straightforward movement compared to AGS cells. The function of tight junction proteins known to E-cadherin expression were evaluated for cell migration by knockdown using sh-RNA. Cell migration and straight movement of EC96 cells were reduced by knockdown of ZO-1 and claudin-7, to a lesser degree. Analysis of the migratory activity of boundary cells and inner cells shows that EC96 cell migration was primarily conducted by boundary cells, similar to leader cells in collective migration. Immunofluorescence analysis showed that tight junctions (TJs) of EC96 cells might play important roles in intracellular communication among boundary cells. ZO-1 is localized to the base of protruding lamellipodia and cell contact sites at the rear of cells, indicating that ZO-1 might be important for the interaction between traction and tensile forces. Overall, dynamic regulation of E-cadherin expression and localization by interaction with ZO-1 protein is one of the targets for elucidating the mechanism of collective migration of cancer metastasis.

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