scholarly journals Substrate mediated elastic coupling between motile cells modulates inter–cell interactions and enhances cell–cell contact

2021 ◽  
Author(s):  
Subhaya Bose ◽  
Kinjal Dasbiswas ◽  
Arvind Gopinath
Keyword(s):  
Cell Motility ◽  
Single Cells ◽  
Cell Structure ◽  
Control Cell ◽  
Cell Interactions ◽  
Biophysical Model ◽  
Cell Contact ◽  
Motile Cells ◽  
Key Aspects ◽  
Cell Cell

AbstractThe mechanical micro–environment of cells and tissues influences key aspects of cell structure and function including cell motility. For proper tissue development, cells need to migrate, interact with other neighbouring cells and form contacts, each of which require the cell to exert physical forces. Cells are known to exert contractile forces on underlying soft substrates. These stresses result in substrate deformation that can affect migratory behavior of cells as well as provide an avenue for cells to sense each other and coordinate their motion. The role of substrate mechanics, particularly its stiffness, in such biological processesis therefore a subject of active investigation. Recent progress in experimental techniques have enabled key insights into pairwise mechanical interactions that control cell motility when they move on compliant soft substrates. Analysis and modeling of such systemsis however still in its nascent stages. Motivated by the role modeling is expected to play in interpreting, informing and guiding experiments, we build a biophysical model for cell migration and cell–cell interactions. Our focus is on situations highly relevant to tissue engineering and regenerative medicine –when substrate traction stresses induced by motile cells enable substrate deformation and serve as a medium of communication. Using a generalizable agent–basedmodel, we compute key metrics of cell motile behavior such as the number of cell–cell contacts over a given time, dispersion of cell trajectories, and probability of permanent cell contact, and analyze how these depend on a cell motility parameter and on substrate stiffness. Our results provide a framework towards modeling the manner in which cells may sense each other mechanically via the substrate and use this information to generate coordinated movements across much longer length scales. Our results also provide a foundation to analyze experiments on the phenomenon known as durotaxis where single cells move preferentially towards regions of high stiffness on patterned substrates.

scholarly journals Matrix Stiffness Modulates Mechanical Interactions and Promotes Contact between Motile Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 428
Author(s):  
Subhaya Bose ◽  
Kinjal Dasbiswas ◽  
Arvind Gopinath
Keyword(s):  
Cell Motility ◽  
Cell Structure ◽  
Biophysical Model ◽  
Cell Contact ◽  
Mechanical Deformations ◽  
Range Cell ◽  
Permanent Cell ◽  
Key Aspects ◽  
And Function ◽  
Cell Cell

The mechanical micro-environment of cells and tissues influences key aspects of cell structure and function, including cell motility. For proper tissue development, cells need to migrate, interact, and form contacts. Cells are known to exert contractile forces on underlying soft substrates and sense deformations in them. Here, we propose and analyze a minimal biophysical model for cell migration and long-range cell–cell interactions through mutual mechanical deformations of the substrate. We compute key metrics of cell motile behavior, such as the number of cell-cell contacts over a given time, the dispersion of cell trajectories, and the probability of permanent cell contact, and analyze how these depend on a cell motility parameter and substrate stiffness. Our results elucidate how cells may sense each other mechanically and generate coordinated movements and provide an extensible framework to further address both mechanical and short-range biophysical interactions.

scholarly journals SyNPL: Synthetic Notch pluripotent cell lines to monitor and manipulate cell interactions in vitro and in vivo

2021 ◽  
Author(s):  
Mattias Malaguti ◽  
Rosa Portero Migueles ◽  
Jennifer Annoh ◽  
Daina Sadurska ◽  
Guillaume Blin ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Lines ◽  
Modular Design ◽  
Cell Interactions ◽  
Cell Populations ◽  
Cell Contact ◽  
Pluripotent Cells ◽  
Cell Fate Decisions ◽  
Cell Cell

ABSTRACTCell-cell interactions govern differentiation and cell competition in pluripotent cells during early development, but the investigation of such processes is hindered by a lack of efficient analysis tools. Here we introduce SyNPL: clonal pluripotent stem cell lines which employ optimised Synthetic Notch (SynNotch) technology to report cell-cell interactions between engineered “sender” and “receiver” cells in cultured pluripotent cells and chimaeric mouse embryos. A modular design makes it straightforward to adapt the system for programming differentiation decisions non-cell-autonomously in receiver cells in response to direct contact with sender cells. We demonstrate the utility of this system by enforcing neuronal differentiation at the boundary between two cell populations. In summary, we provide a new tool which could be used to identify cell interactions and to profile changes in gene or protein expression that result from direct cell-cell contact with defined cell populations in culture and in early embryos, and which can be adapted to generate synthetic patterning of cell fate decisions.

Low-affinity LFA-1/ICAM-3 interactions augment LFA-1/ICAM-1-mediated T cell adhesion and signaling by redistribution of LFA-1

2000 ◽  
Vol 113 (3) ◽  
pp. 391-400 ◽  
Author(s):  
D.A. Bleijs ◽  
M.E. Binnerts ◽  
S.J. van Vliet ◽  
C.G. Figdor ◽  
Y. van Kooyk
Keyword(s):  
T Cell ◽  
Cell Interactions ◽  
T Cell Proliferation ◽  
Cell Contact ◽  
Surface Distribution ◽  
Affinity Ligand ◽  
Large Clusters ◽  
High Affinity Ligand ◽  
Cell Cell

Although ICAM-3 is implicated in both adhesion and signal transduction events of leukocytes, its low affinity for LFA-1 compared to other ligands of LFA-1 has puzzled many investigators. Here we investigated the role of ICAM-3 in supporting LFA-1-mediated ICAM-1 binding and subsequently cell signaling. We observed that although ICAM-3 binds poorly to LFA-1 expressed on resting T cells, it specifically facilitates and increases LFA-1-mediated adhesion to the high affinity ligand of LFA-1, ICAM-1. We demonstrate that low-affinity binding of LFA-1 to ICAM-3 together with ICAM-1 alters the cell surface distribution of LFA-1 dramatically, inducing large clusters of LFA-1 that facilitate ICAM-1 binding after LFA-1 activation. We found that LFA-1-mediated ICAM-1 cell-cell interactions such as T cell proliferation greatly depend on low affinity LFA-1/ICAM-3 interactions that enhance stable LFA-1/ICAM-1 cell-cell contact. Taken together, these data demonstrate that low affinity LFA-1 binding to ICAM-3 regulates strong LFA-1/ICAM-1-mediated adhesion by driving LFA-1 into clusters to facilitate cell-cell interactions that take place in the immune system.

scholarly journals Classical cadherins control nucleus and centrosome position and cell polarity

2009 ◽  
Vol 185 (5) ◽  
pp. 779-786 ◽  
Author(s):  
Isabelle Dupin ◽  
Emeline Camand ◽  
Sandrine Etienne-Manneville
Keyword(s):  
Cell Polarity ◽  
Control Cell ◽  
Cell Types ◽  
Free Cell ◽  
Cell Polarization ◽  
Cell Interactions ◽  
Spatial Cues ◽  
Cell Contacts ◽  
Classical Cadherins ◽  
Cell Cell

Control of cell polarity is crucial during tissue morphogenesis and renewal, and depends on spatial cues provided by the extracellular environment. Using micropatterned substrates to impose reproducible cell–cell interactions, we show that in the absence of other polarizing cues, cell–cell contacts are the main regulator of nucleus and centrosome positioning, and intracellular polarized organization. In a variety of cell types, including astrocytes, epithelial cells, and endothelial cells, calcium-dependent cadherin-mediated cell–cell interactions induce nucleus and centrosome off-centering toward cell–cell contacts, and promote orientation of the nucleus–centrosome axis toward free cell edges. Nucleus and centrosome off-centering is controlled by N-cadherin through the regulation of cell interactions with the extracellular matrix, whereas the orientation of the nucleus–centrosome axis is determined by the geometry of N-cadherin–mediated contacts. Our results demonstrate that in addition to the specific function of E-cadherin in regulating baso-apical epithelial polarity, classical cadherins control cell polarization in otherwise nonpolarized cells.

scholarly journals Learning the dynamics of cell–cell interactions in confined cell migration

2021 ◽  
Vol 118 (7) ◽  
pp. e2016602118 ◽  
Author(s):  
David B. Brückner ◽  
Nicolas Arlt ◽  
Alexandra Fink ◽  
Pierre Ronceray ◽  
Joachim O. Rädler ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Single Cells ◽  
Cell Types ◽  
Theoretical Description ◽  
Cell Interactions ◽  
Cellular Interaction ◽  
Migration Dynamics ◽  
Interaction Behaviors ◽  
Cell Trajectories ◽  
Cell Cell

The migratory dynamics of cells in physiological processes, ranging from wound healing to cancer metastasis, rely on contact-mediated cell–cell interactions. These interactions play a key role in shaping the stochastic trajectories of migrating cells. While data-driven physical formalisms for the stochastic migration dynamics of single cells have been developed, such a framework for the behavioral dynamics of interacting cells still remains elusive. Here, we monitor stochastic cell trajectories in a minimal experimental cell collider: a dumbbell-shaped micropattern on which pairs of cells perform repeated cellular collisions. We observe different characteristic behaviors, including cells reversing, following, and sliding past each other upon collision. Capitalizing on this large experimental dataset of coupled cell trajectories, we infer an interacting stochastic equation of motion that accurately predicts the observed interaction behaviors. Our approach reveals that interacting noncancerous MCF10A cells can be described by repulsion and friction interactions. In contrast, cancerous MDA-MB-231 cells exhibit attraction and antifriction interactions, promoting the predominant relative sliding behavior observed for these cells. Based on these experimentally inferred interactions, we show how this framework may generalize to provide a unifying theoretical description of the diverse cellular interaction behaviors of distinct cell types.

scholarly journals Predicting global dynamics of spatial microbial communities from local interaction rules

2020 ◽  
Author(s):  
Simon van Vliet ◽  
Christoph Hauert ◽  
Martin Ackermann ◽  
Alma Dal Co
Keyword(s):  
Growth Rate ◽  
Microbial Communities ◽  
Molecular Mechanisms ◽  
Single Cells ◽  
Cell Types ◽  
Cell Interactions ◽  
Community Level ◽  
Global Dynamics ◽  
Mathematical Framework ◽  
Cell Cell

AbstractInteractions between cells drive biological processes across all of life, from microbes in the environment to cells in multicellular organisms. Interactions often arise in spatially structured settings, where cells mostly interact with their neighbors. A central question is how the properties of biological systems emerge from local interactions. This question is very relevant in the context of microbial communities, such as biofilms, where cells live close by in space and are connected via a dense network of biochemical interactions. To understand and control the functioning of these communities, it is essential to uncover how community-level properties, such as the community composition, spatial arrangement, and growth rate, arise from these interactions. Here, we develop a mathematical framework that can predict community-level properties from the molecular mechanisms underlying the cell-cell interactions for systems consisting of two cell types. Our predictions match quantitative measurements from an experimental cross-feeding community. For these cross-feeding communities, the community growth rate is reduced when cells interact only with few neighbors; as a result, some communities can co-exist in a well-mixed system, but not in a spatial one. In general, our framework shows that key molecular parameters underlying the cell-cell interactions (e.g. the uptake and leakage rates of molecules) determine community level properties. Our framework can be extended to a variety of systems of two interacting cell types, within and beyond the microbial world, and contributes to our understanding of how biological functions arise from interactions between single cells.

scholarly journals The CEACAM1-L Glycoprotein Associates with the Actin Cytoskeleton and Localizes to Cell–Cell Contact through Activation of Rho-like GTPases

2000 ◽  
Vol 11 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Svetlana Sadekova ◽  
Nathalie Lamarche-Vane ◽  
Xiaodong Li ◽  
Nicole Beauchemin
Keyword(s):  
Cell Adhesion ◽  
Actin Cytoskeleton ◽  
Adhesion Molecule ◽  
Control Cell ◽  
Growth Inhibitor ◽  
Cytoplasmic Domain ◽  
Cell Contact ◽  
A Cell ◽  
Rho Family ◽  
Cell Cell

Associations between plasma membrane-linked proteins and the actin cytoskeleton play a crucial role in defining cell shape and determination, ensuring cell motility and facilitating cell–cell or cell–substratum adhesion. Here, we present evidence that CEACAM1-L, a cell adhesion molecule of the carcinoembryonic antigen family, is associated with the actin cytoskeleton. We have delineated the regions involved in actin cytoskeleton association to the distal end of the CEACAM1-L long cytoplasmic domain. We have demonstrated that CEACAM1-S, an isoform of CEACAM1 with a truncated cytoplasmic domain, does not interact with the actin cytoskeleton. In addition, a major difference in subcellular localization of the two CEACAM1 isoforms was observed. Furthermore, we have established that the localization of CEACAM1-L at cell–cell boundaries is regulated by the Rho family of GTPases. The retention of the protein at the sites of intercellular contacts critically depends on homophilic CEACAM1–CEACAM1 interactions and association with the actin cytoskeleton. Our results provide new evidence on how the Rho family of GTPases can control cell adhesion: by directing an adhesion molecule to its proper cellular destination. In addition, these results provide an insight into the mechanisms of why CEACAM1-L, but not CEACAM1-S, functions as a tumor cell growth inhibitor.

scholarly journals Regulation of Endothelial Cell Motility by Complexes of Tetraspan Molecules CD81/TAPA-1 and CD151/PETA-3 with α3β1 Integrin Localized at Endothelial Lateral Junctions

1998 ◽  
Vol 141 (3) ◽  
pp. 791-804 ◽  
Author(s):  
María Yáñez-Mó ◽  
Arántzazu Alfranca ◽  
Carlos Cabañas ◽  
Mónica Marazuela ◽  
Reyes Tejedor ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Cell Motility ◽  
Cell Polarization ◽  
Cell Junctions ◽  
Cell Junction ◽  
Cell Contact ◽  
Collagen Gels ◽  
Α3β1 Integrin ◽  
Cell Cell

Cell-to-cell junction structures play a key role in cell growth rate control and cell polarization. In endothelial cells (EC), these structures are also involved in regulation of vascular permeability and leukocyte extravasation. To identify novel components in EC intercellular junctions, mAbs against these cells were produced and selected using a morphological screening by immunofluorescence microscopy. Two novel mAbs, LIA1/1 and VJ1/16, specifically recognized a 25-kD protein that was selectively localized at cell–cell junctions of EC, both in the primary formation of cell monolayers and when EC reorganized in the process of wound healing. This antigen corresponded to the recently cloned platelet-endothelial tetraspan antigen CD151/PETA-3 (platelet-endothelial tetraspan antigen-3), and was consistently detected at EC cell–cell contact sites. In addition to CD151/PETA-3, two other members of the tetraspan superfamily, CD9 and CD81/ TAPA-1 (target of antiproliferative antibody-1), localized at endothelial cell-to-cell junctions. Biochemical analysis demonstrated molecular associations among tetraspan molecules themselves and those of CD151/ PETA-3 and CD9 with α3β1 integrin. Interestingly, mAbs directed to both CD151/PETA-3 and CD81/ TAPA-1 as well as mAb specific for α3 integrin, were able to inhibit the migration of ECs in the process of wound healing. The engagement of CD151/PETA-3 and CD81/TAPA-1 inhibited the movement of individual ECs, as determined by quantitative time-lapse video microscopy studies. Furthermore, mAbs against the CD151/PETA-3 molecule diminished the rate of EC invasion into collagen gels. In addition, these mAbs were able to increase the adhesion of EC to extracellular matrix proteins. Together these results indicate that CD81/TAPA-1 and CD151/PETA-3 tetraspan molecules are components of the endothelial lateral junctions implicated in the regulation of cell motility, either directly or by modulation of the function of the associated integrin heterodimers.

scholarly journals Growth kinetics and power laws indicate distinct mechanisms of cell-cell interactions in the aggregation process

2021 ◽  
Author(s):  
Debangana Mukhopadhyay ◽  
Rumi De
Keyword(s):  
Growth Kinetics ◽  
Single Cells ◽  
Domain Size ◽  
Power Laws ◽  
Theoretical Work ◽  
Cell Interactions ◽  
Specific Cell ◽  
Aggregation Process ◽  
Chemical Signalling ◽  
Cell Cell

Cellular aggregation is a complex process orchestrated by various kinds of interactions depending on its environments. Different interactions give rise to different pathways of cellular rearrangement and the development of specialized tissues. To distinguish the underlying mechanisms, in this theoretical work, we investigate the spontaneous emergence of tissue patterns from an ensemble of single cells on a substrate following three leading pathways of cell-cell interactions, namely, direct cell adhesion contacts, matrix mediated mechanical interaction, and chemical signalling. Our analysis shows that the growth kinetics of the aggregation process is distinctly different for each pathway and bears the signature of the specific cell-cell interactions. Interestingly, we find that the average domain size and the mass of the clusters exhibit a power law growth in time under certain interaction mechanisms hitherto unexplored. Further, as observed in experiments, the cluster size distribution can be characterized by stretched exponential functions showing distinct cellular organization processes.

scholarly journals Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity.

1991 ◽  
Vol 115 (5) ◽  
pp. 1383-1395 ◽  
Author(s):  
C H Streuli ◽  
N Bailey ◽  
M J Bissell
Keyword(s):  
Gene Expression ◽  
Basement Membrane ◽  
Single Cells ◽  
Mammary Epithelial ◽  
Cell Contact ◽  
Specific Gene ◽  
Tissue Specific Gene ◽  
Morphological Polarity ◽  
Beta Casein ◽  
Cell Cell

Functional differentiation in mammary epithelia requires specific hormones and local environmental signals. The latter are provided both by extracellular matrix and by communication with adjacent cells, their action being intricately connected in what appears to be a cascade of events leading to milk production. To distinguish between the influence of basement membrane and that of cell-cell contact in this process, we developed a novel suspension culture assay in which mammary epithelial cells were embedded inside physiological substrata. Single cells, separated from each other, were able to assimilate information from a laminin-rich basement membrane substratum and were induced to express beta-casein. In contrast, a stromal environment of collagen I was not sufficient to induce milk synthesis unless accompanied by cell-cell contact. The expression of milk proteins did not depend on morphological polarity since E-cadherin and alpha 6 integrin were distributed evenly around the surface of single cells. In medium containing 5 microM Ca2+, cell-cell interactions were impaired in small clusters and E-cadherin was not detected at the cell surface, yet many cells were still able to produce beta-casein. Within the basement membrane substratum, signal transfer appeared to be mediated through integrins since a function-blocking anti-integrin antibody severely diminished the ability of suspension-cultured cells to synthesize beta-casein. These results provide evidence for a central role of basement membrane in the induction of tissue-specific gene expression.

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