scholarly journals Anomalous Diffusion as a Descriptive Model of Cell Migration

2017 ◽  
Author(s):  
Igor D. Luzhanskey ◽  
John P. MacMunn ◽  
Joshua D. Cohen ◽  
Lauren E. Barney ◽  
Lauren E. Jansen ◽  
...  
Keyword(s):  
Cell Migration ◽  
Anomalous Diffusion ◽  
Mean Square Displacement ◽  
Cell Movement ◽  
Model Parameters ◽  
Time Interval ◽  
Porous Scaffolds ◽  
Mean Square ◽  
3D Environments

AbstractAppropriately chosen descriptive models of cell migration in biomaterials will allow researchers to characterize and ultimately predict the movement of cells in engineered systems for a variety of applications in tissue engineering. The persistent random walk (PRW) model accurately describes cell migration on two-dimensional (2D) substrates. However, this model inherently cannot describe subdiffusive cell movement, i.e. migration paths in which the root mean square displacement increases more slowly than the square root of the time interval. Subdiffusivity is a common characteristic of cells moving in confined environments, such as three-dimensional (3D) porous scaffolds, hydrogel networks, and in vivo tissues. We demonstrate that a generalized anomalous diffusion (AD) model, which uses a simple power law to relate the mean square displacement (MSD) to time, more accurately captures individual cell migration paths across a range of engineered 2D and 3D environments than does the more commonly used PRW model. We used the AD model parameters to distinguish cell movement profiles on substrates with different chemokinetic factors, geometries (2D vs 3D), substrate adhesivities, and compliances. Although the two models performed with equal precision for superdiffusive cells, we suggest a simple AD model, in lieu of PRW, to describe cell trajectories in populations with a significant subdiffusive fraction, such as cells in confined, 3D environments.

scholarly journals 2D or 3D? How in vitro cell motility is conserved across dimensions, and predicts in vivo invasion

2019 ◽  
Author(s):  
Sualyneth Galarza ◽  
Hyuna Kim ◽  
Naciye Atay ◽  
Shelly R Peyton ◽  
Jennifer M Munson
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Cell Movement ◽  
Complex Model ◽  
Model Systems ◽  
Cellular Motility ◽  
Statistical Tool ◽  
3D Environments

AbstractCell motility is a critical aspect of wound healing, the immune response, and is deregulated in cancer. Current limitations in imaging tools make it difficult to study cell migration in vivo. To overcome this, and to identify drivers from the microenvironment that regulate cell migration, bioengineers have developed 2D and 3D tissue model systems in which to study cell motility in vitro, with the aim of mimicking the environments in which cells move in vivo. However, there has been no systematic study to explicitly relate and compare cell motility measurements between these geometries/systems. Here, we provide such analysis on our own data, as well as across data in existing literature to understand whether, and which, in vitro models are predictive of in vivo cell motility. To our surprise, many metrics of cell movement on 2D surfaces significantly and positively correlate with cell migration in 3D environments, and cell invasion in 3D is negatively correlated with glioblastoma invasion in vivo. Finally, to best compare across complex model systems, in vivo data, and data from different labs, we suggest that groups report an effect size, a statistical tool that is most translatable across experiments and labs, when conducting experiments that affect cellular motility.

scholarly journals Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA leading to localized inhibition of contractility

2006 ◽  
Vol 176 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Erik Sahai ◽  
Raquel Garcia-Medina ◽  
Jacques Pouysségur ◽  
Emmanuel Vial
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Rho Gtpases ◽  
Rho Kinase ◽  
Cell Movement ◽  
Leading Edge ◽  
Cell Periphery ◽  
Tumor Cell Migration ◽  
Tumor Cell Motility

Rho GTPases participate in various cellular processes, including normal and tumor cell migration. It has been reported that RhoA is targeted for degradation at the leading edge of migrating cells by the E3 ubiquitin ligase Smurf1, and that this is required for the formation of protrusions. We report that Smurf1-dependent RhoA degradation in tumor cells results in the down-regulation of Rho kinase (ROCK) activity and myosin light chain 2 (MLC2) phosphorylation at the cell periphery. The localized inhibition of contractile forces is necessary for the formation of lamellipodia and for tumor cell motility in 2D tissue culture assays. In 3D invasion assays, and in in vivo tumor cell migration, the inhibition of Smurf1 induces a mesenchymal–amoeboid–like transition that is associated with a more invasive phenotype. Our results suggest that Smurf1 is a pivotal regulator of tumor cell movement through its regulation of RhoA signaling.

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 WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment

2018 ◽  
Vol 115 (34) ◽  
pp. 8581-8586 ◽  
Author(s):  
Pengbo Wang ◽  
Marcel Dreger ◽  
Elena Madrazo ◽  
Craig J. Williams ◽  
Rafael Samaniego ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Underlying Mechanism ◽  
H3k4 Methylation ◽  
Nuclear Mechanics ◽  
3D Environment ◽  
3D Environments ◽  
And Migration

Cell migration through extracellular matrices requires nuclear deformation, which depends on nuclear stiffness. In turn, chromatin structure contributes to nuclear stiffness, but the mechanosensing pathways regulating chromatin during cell migration remain unclear. Here, we demonstrate that WD repeat domain 5 (WDR5), an essential component of H3K4 methyltransferase complexes, regulates cell polarity, nuclear deformability, and migration of lymphocytes in vitro and in vivo, independent of transcriptional activity, suggesting nongenomic functions for WDR5. Similarly, depletion of RbBP5 (another H3K4 methyltransferase subunit) promotes similar defects. We reveal that a 3D environment increases the H3K4 methylation dependent on WDR5 and results in a globally less compacted chromatin conformation. Further, using atomic force microscopy, nuclear particle tracking, and nuclear swelling experiments, we detect changes in nuclear mechanics that accompany the epigenetic changes induced in 3D conditions. Indeed, nuclei from cells in 3D environments were softer, and thereby more deformable, compared with cells in suspension or cultured in 2D conditions, again dependent on WDR5. Dissecting the underlying mechanism, we determined that actomyosin contractility, through the phosphorylation of myosin by MLCK (myosin light chain kinase), controls the interaction of WDR5 with other components of the methyltransferase complex, which in turn up-regulates H3K4 methylation activation in 3D conditions. Taken together, our findings reveal a nongenomic function for WDR5 in regulating H3K4 methylation induced by 3D environments, physical properties of the nucleus, cell polarity, and cell migratory capacity.

scholarly journals Lecture on the anomalous diffusion in Condensed Matter Physics

2018 ◽  
Vol 3 (2) ◽  
Author(s):  
M. Benhamou ◽  
Keyword(s):  
Anomalous Diffusion ◽  
Condensed Matter ◽  
Mean Square Displacement ◽  
Continuous Phase ◽  
Generalized Langevin Equation ◽  
Velocity Autocorrelation Function ◽  
Condensed Matter Physics ◽  
Mean Square ◽  
Pickering Emulsions ◽  
The Mean

Diffusion is a natural or artificial process that governs many phenomena in nature. The most known diffusion is the Brownian or normal motion, where the mean-square-displacement of the tracer (diffusive particle among others) increases as the square-root of time. It is not the case, however, for complex systems, where the diffusion is rather slow, because at small-scales, these media present an heterogenous structure. This kind of slow motion is called subdiffusion, where the associated mean-square-displacement increases in time, with a non trivial exponent, alpha, whose value is between 0 and 1. In this review paper, we report on new trends dealing with the study of the anomalous diffusion in Condensed Matter Physics. The study is achieved using a theoretical approach that is based on a Generalized Langevin Equation. As particular crowded systems, we choose the so-called Pickering emulsions (oil-in-water), and we are interested in how the dispersed droplets (protected by small solid charged nanoparticles) can diffuse in the continuous phase (water). Dynamic study is accomplished through the mean-square-displacement and the velocity-autocorrelation-function. Finally, a comparison with Molecular Dynamics data is made.

scholarly journals Fluid-flow-induced mesenchymal stem cell migration: role of focal adhesion kinase and RhoA kinase sensors

2015 ◽  
Vol 12 (104) ◽  
pp. 20141351 ◽  
Author(s):  
Brandon D. Riehl ◽  
Jeong Soon Lee ◽  
Ligyeom Ha ◽  
Jung Yul Lim
Keyword(s):  
Stem Cell ◽  
Cell Migration ◽  
Mesenchymal Stem Cell ◽  
Focal Adhesion ◽  
Mean Square Displacement ◽  
Mean Square ◽  
Flow Conditions ◽  
Rhoa Kinase ◽  
Cytoskeletal Tension

The study of mesenchymal stem cell (MSC) migration under flow conditions with investigation of the underlying molecular mechanism could lead to a better understanding and outcome in stem-cell-based cell therapy and regenerative medicine. We used peer-reviewed open source software to develop methods for efficiently and accurately tracking, measuring and processing cell migration as well as morphology. Using these tools, we investigated MSC migration under flow-induced shear and tested the molecular mechanism with stable knockdown of focal adhesion kinase (FAK) and RhoA kinase (ROCK). Under steady flow, MSCs migrated following the flow direction in a shear stress magnitude-dependent manner, as assessed by root mean square displacement and mean square displacement, motility coefficient and confinement ratio. Silencing FAK in MSCs suppressed morphology adaptation capability and reduced cellular motility for both static and flow conditions. Interestingly, ROCK silencing significantly increased migration tendency especially under flow. Blocking ROCK, which is known to reduce cytoskeletal tension, may lower the resistance to skeletal remodelling during the flow-induced migration. Our data thus propose a potentially differential role of focal adhesion and cytoskeletal tension signalling elements in MSC migration under flow shear.

scholarly journals Adapting the Pore Size of Individual, 3D-Printed CPC Scaffolds in Maxillofacial Surgery

2021 ◽  
Vol 10 (12) ◽  
pp. 2654
Author(s):  
David Muallah ◽  
Philipp Sembdner ◽  
Stefan Holtzhausen ◽  
Heike Meissner ◽  
André Hutsky ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Cell Migration ◽  
Pore Size ◽  
High Pressures ◽  
Maxillofacial Surgery ◽  
Patient Specific ◽  
Porous Scaffolds ◽  
Bone Augmentation ◽  
3D Printed

Three dimensional (3D) printing allows additive manufacturing of patient specific scaffolds with varying pore size and geometry. Such porous scaffolds, made of 3D-printable bone-like calcium phosphate cement (CPC), are suitable for bone augmentation due to their benefit for osteogenesis. Their pores allow blood-, bone- and stem cells to migrate, colonize and finally integrate into the adjacent tissue. Furthermore, the pore size affects the scaffold’s stability. Since scaffolds in maxillofacial surgery have to withstand high forces within the jaw, adequate mechanical properties are of high clinical importance. Although many studies have investigated CPC for bone augmentation, the ideal porosity for specific indications has not been defined yet. We investigated 3D printed CPC cubes with increasing pore sizes and different printing orientations regarding cell migration and mechanical properties in comparison to commercially available bone substitutes. Furthermore, by investigating clinical cases, the scaffolds’ designs were adapted to resemble the in vivo conditions as accurately as possible. Our findings suggest that the pore size of CPC scaffolds for bone augmentation in maxillofacial surgery necessarily needs to be adapted to the surgical site. Scaffolds for sites that are not exposed to high forces, such as the sinus floor, should be printed with a pore size of 750 µm to benefit from enhanced cell infiltration. In contrast, for areas exposed to high pressures, such as the lateral mandible, scaffolds should be manufactured with a pore size of 490 µm to guarantee adequate cell migration and in order to withstand the high forces during the chewing process.

scholarly journals A high-throughput 3D bioprinted cancer cell migration and invasion model with versatile and broad biological applicability

2021 ◽  
Author(s):  
MoonSun Jung ◽  
Joanna Skhinas ◽  
Eric Y Du ◽  
Maria Kristine Tolentino ◽  
Robert Utama ◽  
...  
Keyword(s):  
Cell Migration ◽  
High Throughput ◽  
Drug Screening ◽  
Cancer Biology ◽  
Cell Movement ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Drop On Demand

Understanding the underlying mechanisms of migration and metastasis is a key focus of cancer research. There is an urgent need to develop in vitro 3D tumor models that can mimic physiological cell-cell and cell-extracellular matrix interactions, with high reproducibility and that are suitable for high throughput (HTP) drug screening. Here, we developed a HTP 3D bioprinted migration model using a bespoke drop-on-demand bioprinting platform. This HTP platform coupled with tunable hydrogel systems enables (i) the rapid encapsulation of cancer cells within in vivo tumor mimicking matrices, (ii) in situ and real-time measurement of cell movement, (iii) detailed molecular analysis for the study of mechanisms underlying cell migration and invasion, and (iv) the identification of novel therapeutic options. This work demonstrates that this HTP 3D bioprinted cell migration platform has broad applications across quantitative cell and cancer biology as well as drug screening.

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 Inferring Active Noise Characteristics from the Paired Observations of Anomalous Diffusion

Polymers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 2 ◽  
Author(s):  
Takuya Saito ◽  
Takahiro Sakaue
Keyword(s):  
Momentum Transfer ◽  
Anomalous Diffusion ◽  
Mean Square Displacement ◽  
The Other ◽  
Mean Square ◽  
Equilibrium Relation ◽  
Time Integral ◽  
Noise Characteristics ◽  
Active Noise ◽  
The Mean

Anomalous diffusion has been most often argued in terms of a position fluctuation of a tracer. We here propose the other fluctuating observable, i.e., momentum transfer defined as the time integral of applied force to hold a tracer’s position. Being a conjugated variable, the momentum transfer is thought of as generating the anomalous diffusion paired with the position’s one. By putting together the paired anomalous diffusions, we aim to extract useful information in complex systems, which can be applied to experiments like tagged monomer observations in chromatin. The polymer being in the equilibrium, the mean square displacement (or variance) of position displacement or momentum transfer exhibits the sub- or superdiffusion, respectively, in which the sum of the anomalous diffusion indices is conserved quite generally, but the nonequilibrium media that generate the active noise may manifest the derivations from the equilibrium relation. We discuss the deviations that reflect the characteristics of the active noise.

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