Viscoelastic relaxation of collagen networks provides a self-generated directional cue during collective migration

2020 ◽  
Author(s):  
Andrew G. Clark ◽  
Ananyo Maitra ◽  
Cécile Jacques ◽  
Anthony Simon ◽  
Carlos Pérez-González ◽  
...  
Keyword(s):  
Short Range ◽  
Single Cells ◽  
Chemical Crosslinking ◽  
Viscoelastic Relaxation ◽  
Collective Migration ◽  
Cellular Environment ◽  
Migration Dynamics ◽  
Internal Polarity ◽  
Small Clusters ◽  
Theory And Experiments

AbstractThere is growing evidence that the physical properties of the cellular environment can impact cell migration. However, it is not currently understood how active physical remodeling of the network by cells affects their migration dynamics. Here, we study collective migration of small clusters of cells on deformable collagen-1 networks. Combining theory and experiments, we find that cell clusters, despite displaying no apparent internal polarity, migrate persistently and generate asymmetric collagen gradients during migration. We find that persistent migration can arise from viscoelastic relaxation of collagen networks, and reducing the viscoelastic relaxation time by chemical crosslinking leads to a reduction in migration persistence. Single cells produce only short range network deformations that relax on shorter timescales, which leads to lower migration persistence. This physical model provides a mechanism for self-generated directional migration on viscoelastic substrates in the absence of internal biochemical cues.

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 Animal simulations facilitate smart drug design through prediction of nanomaterial transport to individual tissue cells

2020 ◽  
Vol 6 (4) ◽  
pp. eaax2642 ◽  
Author(s):  
Edward Price ◽  
Andre J. Gesquiere
Keyword(s):  
Drug Design ◽  
Fluid Dynamic ◽  
Single Cells ◽  
Whole Body ◽  
Target Tissue ◽  
Vitro Assay ◽  
Cellular Environment ◽  
Tissue Cells ◽  
Smart Drug

Smart drug design for antibody and nanomaterial-based therapies allows optimization of drug efficacy and more efficient early-stage preclinical trials. The ideal drug must display maximum efficacy at target tissue sites, with transport from tissue vasculature to the cellular environment being critical. Biological simulations, when coupled with in vitro approaches, can predict this exposure in a rapid and efficient manner. As a result, it becomes possible to predict drug biodistribution within single cells of live animal tissue without the need for animal studies. Here, we successfully utilized an in vitro assay and a computational fluid dynamic model to translate in vitro cell kinetics (accounting for cell-induced degradation) to whole-body simulations for multiple species as well as nanomaterial types to predict drug distribution into individual tissue cells. We expect this work to assist in refining, reducing, and replacing animal testing, while providing scientists with a new perspective during the drug development process.

The inferior medullary velum: anatomical study and neurosurgical relevance

2013 ◽  
Vol 118 (2) ◽  
pp. 315-318 ◽  
Author(s):  
R. Shane Tubbs ◽  
Anand N. Bosmia ◽  
Marios Loukas ◽  
Eyas M. Hattab ◽  
Aaron A. Cohen-Gadol
Keyword(s):  
Average Length ◽  
Single Cells ◽  
Posterior Inferior Cerebellar Artery ◽  
Anatomical Study ◽  
Ependymal Cells ◽  
Middle Cerebellar Peduncle ◽  
Cerebellar Artery ◽  
Cerebellar Peduncle ◽  
Small Clusters ◽  
Immunohistochemical Analyses

Object Although it is often visualized surgically, details regarding the inferior medullary velum are lacking in the literature. The present study is intended to better elucidate this neuroanatomical structure using microsurgical and immunohistochemical analyses. Methods To study the inferior medullary velum, the authors performed microdissection in 15 adult cadavers. Following gross study, specimens were examined histologically. Results The inferior medullary velum extended from the flocculus to the middle cerebellar peduncle and stretched between the inferior cerebellar peduncle and the nodule and pyramid. The average thickness of the velum was found to be 0.5 mm (range 0.35–0.8 mm) and the average length was found to be 6 mm (range 5.5–7.2 mm). Arterial branches were identified in all specimens that arose from medullary branches of the posterior inferior cerebellar artery and supplied the inferior medullary velum. Histologically and from internal to external, a choroid plexus epithelium as a single cell layer was adjacent to a cuboidal layer of ependymal cells with no visible cilia. The next layer contained scattered glia in single cells or small clusters. The most external layer was composed of flat spindle cells resembling fibroblasts. No neurons of any type were identified. Only rare axons traversed the thin hypocellular zone that disappeared toward the midline. Conclusions Based on this cadaveric study, the authors conclude that division of the inferior medullary velum should be relatively harmless as no neuronal cells were identified in this structure, which appears to be a vestigial bridge of tissue between the left and right sides of the cerebellum.

scholarly journals Striking heterogeneity of somatic L1 retrotransposition in single normal and cancerous gastrointestinal cells

2020 ◽  
Vol 117 (51) ◽  
pp. 32215-32222 ◽  
Author(s):  
Katsumi Yamaguchi ◽  
Alisha O. Soares ◽  
Loyal A. Goff ◽  
Anjali Talasila ◽  
Jungbin A. Choi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Cells ◽  
Single Cell Analysis ◽  
Single Cells ◽  
Variable Number ◽  
Normal Tissues ◽  
Modified Method ◽  
Cellular Environment ◽  
Large Numbers ◽  
Cancer Tissues

Somatic LINE-1 (L1) retrotransposition has been detected in early embryos, adult brains, and the gastrointestinal (GI) tract, and many cancers, including epithelial GI tumors. We previously found numerous somatic L1 insertions in paired normal and GI cancerous tissues. Here, using a modified method of single-cell analysis for somatic L1 insertions, we studied adenocarcinomas of colon, pancreas, and stomach, and found a variable number of somatic L1 insertions in tumors of the same type from patient to patient. We detected no somatic L1 insertions in single cells of 5 of 10 tumors studied. In three tumors, aneuploid cells were detected by FACS. In one pancreatic tumor, there were many more L1 insertions in aneuploid than in euploid tumor cells. In one gastric cancer, both aneuploid and euploid cells contained large numbers of likely clonal insertions. However, in a second gastric cancer with aneuploid cells, no somatic L1 insertions were found. We suggest that when the cellular environment is favorable to retrotransposition, aneuploidy predisposes tumor cells to L1 insertions, and retrotransposition may occur at the transition from euploidy to aneuploidy. Seventeen percent of insertions were also present in normal cells, similar to findings in genomic DNA from normal tissues of GI tumor patients. We provide evidence that: 1) The number of L1 insertions in tumors of the same type is highly variable, 2) most somatic L1 insertions in GI cancer tissues are absent from normal tissues, and 3) under certain conditions, somatic L1 retrotransposition exhibits a propensity for occurring in aneuploid cells.

scholarly journals The scar constituent Collagen I triggers coordinated collective migration and invasion in a 3D spheroid model of early endometriotic lesions

2020 ◽  
Author(s):  
Anna Stejskalova ◽  
Victoria Fincke ◽  
Melissa Nowak ◽  
Yvonne Schmidt ◽  
Marie-Kristin von Wahlde ◽  
...  
Keyword(s):  
Stromal Cells ◽  
3D Model ◽  
Single Cells ◽  
Experimental Models ◽  
Collagen I ◽  
Migration And Invasion ◽  
Collective Migration ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells

AbstractEndometriosis is a painful gynaecological condition characterized by ectopic growth of endometrial cells outside of the uterus. Little is known about the mechanisms by which endometrial fragments invade tissues. This is partially due to a lack of suitable experimental models. In this study, we show that a spheroid 3D model, but not single cells mimic the collective endometrial fragment-like invasion through the extracellular matrix. This model reveals that collagen I, the main constituent of surgical scars, significantly increases the rate of lesion formation by healthy endometrial stromal cells (St-T1b) in vitro compared to the basement membrane-like matrix Matrigel. Stromal cell invasion of collagen I requires MMPs, whereas collective migration of endometriotic epithelial 12Z cells involves Rac-signalling. We show that inhibiting ROCK signalling responsible for actomyosin contraction increases the lesion-size. Moreover, endometriotic epithelial 12Z cells, but not eutopic stromal cells St-T1b migrate on Matrigel. The rate of this migration is decreased by the microRNA miR-200b and increased by miR-145. Our 3D model offers a facile approach to dissect how endometrial fragments invade tissues and is an important step toward developing new personalized therapeutics for endometriosis. Moreover, our model is a suitable tool to screen small molecule drugs and microRNA-based therapeutics.

Segmental pattern of development of the hindbrain and spinal cord of the zebrafish embryo

Development ◽  
1988 ◽  
Vol 103 (1) ◽  
pp. 49-58 ◽  
Author(s):  
E. Hanneman ◽  
B. Trevarrow ◽  
W.K. Metcalfe ◽  
C.B. Kimmel ◽  
M. Westerfield
Keyword(s):  
Spinal Cord ◽  
Monoclonal Antibody ◽  
Early Development ◽  
Zebrafish Embryo ◽  
Single Cells ◽  
Acetylcholinesterase Activity ◽  
Zebrafish Embryos ◽  
Small Clusters ◽  
Spinal Motoneurones

In the ventral hindbrain and spinal cord of zebrafish embryos, the first neurones that can be identified appear as single cells or small clusters of cells, distributed periodically at intervals equal to the length of a somite. In the hindbrain, a series of neuromeres of corresponding length is present, and the earliest neurones are located in the centres of each neuromere. Young neurones within both the hindbrain and spinal cord were identified in live embryos using Nomarski optics, and histochemically by labelling for acetylcholinesterase activity and expression of an antigen recognized by the monoclonal antibody zn-1. Among them are individually identified hindbrain reticulospinal neurones and spinal motoneurones. These observations suggest that early development in these regions of the CNS reflects a common segmental pattern. Subsequently, as more neurones differentiate, the initially similar patterning of the cells in these two regions diverges. A continuous longitudinal column of developing neurones appears in the spinal cord, whereas an alternating series of large and small clusters of neurones is present in the hindbrain.

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 Microenvironmental topographic cues influence migration dynamics of nasopharyngeal carcinoma cells from tumour spheroids

RSC Advances ◽  
2020 ◽  
Vol 10 (48) ◽  
pp. 28975-28983
Author(s):  
Bowie P. Lam ◽  
Sarah K. C. Cheung ◽  
Yun W. Lam ◽  
Stella W. Pang
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Carcinoma Cells ◽  
Collective Migration ◽  
Tumour Spheroids ◽  
Migration Dynamics

Investigation of collective migration of nasopharyngeal carcinoma cells from tumour spheroids on micro-engineered platforms that induced asymmetrical tumour shape.

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