Traction Forces During Cell Migration Predicted by the Multiphysics Model

2011 ◽  
Author(s):  
Sangyoon J. Han ◽  
Nathan J. Sniadecki
Keyword(s):  
Computational Models ◽  
Temporal Dynamics ◽  
Focal Adhesions ◽  
Traction Force ◽  
Leading Edge ◽  
Traction Forces ◽  
Spatial And Temporal Dynamics ◽  
Trailing Edges ◽  
Cytoskeletal Tension ◽  
Biochemical Activation

Cells rely on traction forces in order to crawl across a substrate. These traction forces come from dynamic changes in focal adhesions, cytoskeletal structures, and chemical and mechanical signals from the extracellular matrix. Several computational models have been developed that help explain the trajectory or accumulation of cells during migration, but little attention has been placed on traction forces during this process. Here, we investigated the spatial and temporal dynamics of traction forces by using a multiphysics model that describes the cycle of steps for a migrating cell on an array of posts. The migration cycle includes extension of the leading edge, formation of new adhesions at the front, contraction of the cytoskeleton, and the release of adhesions at the rear. In the model, an activation signal triggers the assembly of actin and myosin into a stress fiber, which generates a cytoskeletal tension in a manner similar to Hill’s muscle model. In addition, the role that adhesion dynamics has in regulating cytoskeletal tension has been added to the model. The multiphysics model was simulated in Matlab for 1-D simulations, and in Comsol for 2-D simulations. The model was able to predict the spatial distribution of traction forces observed with previous experiments in which large forces were seen at the leading and trailing edges. The large traction force at the trailing edge during the extension phase likely contributes to detachment of the focal adhesion by overcoming its adhesion strength with the post. Moreover, the model found that the mechanical work of a migrating cell underwent a cyclic relationship that rose with the formation of a new adhesion and fell with the release of an adhesion at its rear. We applied a third activation signal at the time of release and found it helped to maintain a more consistent level of work during migration. Therefore, the results from both our 1-D and 2-D migration simulations strongly suggest that cells use biochemical activation to supplement the loss in cytoskeletal tension upon adhesion release.

Study of Cellular Adhesion by Means of Micropillar Surface Topologies

2011 ◽  
Vol 409 ◽  
pp. 105-110 ◽  
Author(s):  
Francesca Boccafoschi ◽  
Marco Rasponi ◽  
Cecilia Mosca ◽  
Erica Bocchi ◽  
Simone Vesentini
Keyword(s):  
Focal Adhesion ◽  
Vascular Tissue ◽  
Focal Adhesions ◽  
Traction Force ◽  
Cellular Adhesion ◽  
Research Field ◽  
Traction Forces ◽  
Adhesion Sites ◽  
Substrate Rigidity ◽  
Open Question

It is well-known that cellular behavior can be guided by chemical signals and physical interactions at the cell-substrate interface. The patterns that cells encounter in their natural environment include nanometer-to-micrometer-sized topographies comprising extracellular matrix, proteins, and adjacent cells. Whether cells transduce substrate rigidity at the microscopic scale (for example, sensing the rigidity between adhesion sites) or the nanoscopic scale remains an open question. Here we report that micromolded elastomeric micropost arrays can decouple substrate rigidity from adhesive and surface properties. Arrays of poly (dimethylsiloxane) (PDMS) microposts from microfabricated silicon masters have been fabricated. To control substrate rigidity they present the same post heights but different surface area and spacing between posts. The main advantage of micropost arrays over other surface modification solutions (i.e. hydrogels) is that measured subcellular traction forces could be attributed directly to focal adhesions. This would allow to map traction forces to individual focal adhesions and spatially quantify subcellular distributions of focal-adhesion area, traction force and focal-adhesion stress. Moreover, different adhesion intracellular pathways could be used by the cells to differentiate toward a proliferative or a contractile cellular phenotype, for instance. This particular application is advantageous for vascular tissue engineering applications, where mimicking as close as possible the vessels dynamics should be a step forward in this research field.

scholarly journals Studying the Dynamics of Flagella in Multicellular Communities of Escherichia coli by Using Biarsenical Dyes

2009 ◽  
Vol 76 (4) ◽  
pp. 1241-1250 ◽  
Author(s):  
Matthew F. Copeland ◽  
Shane T. Flickinger ◽  
Hannah H. Tuson ◽  
Douglas B. Weibel
Keyword(s):  
Escherichia Coli ◽  
Thin Layer ◽  
Temporal Dynamics ◽  
Leading Edge ◽  
Epifluorescence Microscopy ◽  
New Approach ◽  
Spatial And Temporal Dynamics ◽  
Close Proximity ◽  
Agar Surface ◽  
Transient Interactions

ABSTRACT This paper describes a new approach for labeling intact flagella using the biarsenical dyes FlAsH and ReAsH and imaging their spatial and temporal dynamics on live Escherichia coli cells in swarming communities of bacteria by using epifluorescence microscopy. Using this approach, we observed that (i) bundles of flagella on swarmer cells remain cohesive during frequent collisions with neighboring cells, (ii) flagella on nonmotile swarmer cells at the leading edge of the colony protrude in the direction of the uncolonized agar surface and are actively rotated in a thin layer of fluid that extends outward from the colony, and (iii) flagella form transient interactions with the flagella of other swarmer cells that are in close proximity. This approach opens a window for observing the dynamics of cells in communities that are relevant to ecology, industry, and biomedicine.

scholarly journals Effects of substrate stiffness and actomyosin contractility on coupling between force transmission and vinculin–paxillin recruitment at single focal adhesions

2017 ◽  
Vol 28 (14) ◽  
pp. 1901-1911 ◽  
Author(s):  
Dennis W. Zhou ◽  
Ted T. Lee ◽  
Shinuo Weng ◽  
Jianping Fu ◽  
Andrés J. García
Keyword(s):  
Residence Time ◽  
Focal Adhesions ◽  
Traction Force ◽  
Applied Force ◽  
Substrate Stiffness ◽  
Force Transmission ◽  
Actomyosin Contractility ◽  
Force Transfer ◽  
Cytoskeletal Tension ◽  
The Relationship

Focal adhesions (FAs) regulate force transfer between the cytoskeleton and ECM–integrin complexes. We previously showed that vinculin regulates force transmission at FAs. Vinculin residence time in FAs correlated with applied force, supporting a mechanosensitive model in which forces stabilize vinculin’s active conformation to promote force transfer. In the present study, we examined the relationship between traction force and vinculin–paxillin localization to single FAs in the context of substrate stiffness and actomyosin contractility. We found that vinculin and paxillin FA area did not correlate with traction force magnitudes at single FAs, and this was consistent across different ECM stiffness and cytoskeletal tension states. However, vinculin residence time at FAs varied linearly with applied force for stiff substrates, and this was disrupted on soft substrates and after contractility inhibition. In contrast, paxillin residence time at FAs was independent of local applied force and substrate stiffness. Paxillin recruitment and residence time at FAs, however, were dependent on cytoskeletal contractility on lower substrate stiffness values. Finally, substrate stiffness and cytoskeletal contractility regulated whether vinculin and paxillin turnover dynamics are correlated to each other at single FAs. This analysis sheds new insights on the coupling among force, substrate stiffness, and FA dynamics.

scholarly journals Does cellular adaptation to force loading rate determine the biphasic vs monotonic response of actin retrograde flow with substrate rigidity?

2021 ◽  
Author(s):  
Partho Sakha De ◽  
Rumi De
Keyword(s):  
Cancer Progression ◽  
Loading Rate ◽  
Focal Adhesions ◽  
Traction Force ◽  
Leading Edge ◽  
Substrate Stiffness ◽  
Retrograde Flow ◽  
Force Loading ◽  
Substrate Rigidity ◽  
Cell Traction

AbstractThe transmission of cytoskeletal forces to the extracellular matrix through focal adhesion complexes is essential for a multitude of biological processes such as cell migration, differentiation, tissue development, cancer progression, among others. During migration, focal adhesions arrest the actin retrograde flow towards the cell interior, allowing the cell front to move forward. Here, we address a puzzling observation of the existence of two distinct phenomena: a biphasic relationship of the retrograde flow and cell traction force with increasing substrate rigidity, with maximum traction force and minimum retrograde flow velocity being present at an optimal substrate stiffness; in contrast, a monotonic relationship between them where the retrograde flow decreases and traction force increases with substrate stiffness. We propose a theoretical model for cell-matrix adhesions at the leading edge of a migrating cell, incorporating a novel approach in force loading rate sensitive binding and reinforcement of focal adhesions assembly and the subsequent force-induced slowing down of actin flow. Our model unravels both biphasic and monotonic responses of the retrograde flow and cell traction force with increasing substrate rigidity, owing to the cell’s ability to sense and adapt to the fast-growing forces. Moreover, we also elucidate how the viscoelastic properties of the substrate regulate these nonlinear responses and alter cellular behaviours.

Development of a Novel Magnetic-Driven Micropillar Substrate for Mechanical Stimulation at Individual Focal Adhesions of Cells

2012 ◽  
Author(s):  
Kazuaki Nagayama ◽  
Yasuhiro Hamada ◽  
Takuya Inoue ◽  
Takeo Matsumoto
Keyword(s):  
Mechanical Stimulation ◽  
Essential Role ◽  
Flexible Substrate ◽  
Focal Adhesions ◽  
Traction Force ◽  
Cellular Functions ◽  
Traction Forces ◽  
Local Displacement ◽  
Cellular Mechanotransduction ◽  
Microfabricated Arrays

Traction force generated at focal adhesions (FAs) of cells plays an essential role in regulating various cellular functions. The force can be measured by plating cells on a flexible substrate to observe local displacement of the substrate caused by the forces (1–100 nN) [1]. Approaches employing this method include using microfabricated arrays of poly(dimethylsiloxane) (PDMS) micropillars that bend by cellular traction forces [2]. If you could apply forces to individual FAs independently by actively moving micropillars, it should become a powerful tool to delineate the cellular mechanotransduction mechanisms.

scholarly journals Distinct Roles of Frontal and Rear Cell-Substrate Adhesions in Fibroblast Migration

2001 ◽  
Vol 12 (12) ◽  
pp. 3947-3954 ◽  
Author(s):  
Steven Munevar ◽  
Yu-li Wang ◽  
Micah Dembo
Keyword(s):  
Cell Migration ◽  
Traction Force ◽  
Leading Edge ◽  
Traction Forces ◽  
Passive Resistance ◽  
Fibroblast Migration ◽  
3T3 Fibroblasts ◽  
Cell Substrate ◽  
Extensive Cell ◽  
Physical And Chemical

Cell migration involves complex physical and chemical interactions with the substrate. To probe the mechanical interactions under different regions of migrating 3T3 fibroblasts, we have disrupted cell-substrate adhesions by local application of the GRGDTP peptide, while imaging stress distribution on the substrate with traction force microscopy. Both spontaneous and GRGDTP-induced detachment of the trailing edge caused extensive cell shortening, without changing the overall level of traction forces or the direction of migration. In contrast, disruption of frontal adhesions caused dramatic, global loss of traction forces before any significant shortening of the cell. Although traction forces and cell migration recovered within 10–20 min of transient frontal treatment, persistent treatment with GRGDTP caused the cell to develop traction forces elsewhere and reorient toward a new direction. We conclude that contractile forces of a fibroblast are transmitted to the substrate through two distinct types of adhesions. Leading edge adhesions are unique in their ability to transmit active propulsive forces. Their functions cannot be transferred directly to existing adhesions upon detachment. Trailing end adhesions create passive resistance during cell migration and readily redistribute their loads upon detachment. Our results indicate the distinct nature of mechanical interactions at the leading versus trailing edges, which together generate the mechanical interactions for fibroblast migration.

scholarly journals Cytoskeletal Mechanics Regulating Amoeboid Cell Locomotion

2014 ◽  
Vol 66 (5) ◽  
Author(s):  
Begoña Álvarez-González ◽  
Effie Bastounis ◽  
Ruedi Meili ◽  
Juan C. del Álamo ◽  
Richard Firtel ◽  
...  
Keyword(s):  
Cell Migration ◽  
Traction Force ◽  
Leading Edge ◽  
Cell Types ◽  
Traction Forces ◽  
Amoeboid Cell ◽  
Periodic Movement ◽  
Wide Range ◽  
Motility Cycle ◽  
Wave Complex

Migrating cells exert traction forces when moving. Amoeboid cell migration is a common type of cell migration that appears in many physiological and pathological processes and is performed by a wide variety of cell types. Understanding the coupling of the biochemistry and mechanics underlying the process of migration has the potential to guide the development of pharmacological treatment or genetic manipulations to treat a wide range of diseases. The measurement of the spatiotemporal evolution of the traction forces that produce the movement is an important aspect for the characterization of the locomotion mechanics. There are several methods to calculate the traction forces exerted by the cells. Currently the most commonly used ones are traction force microscopy methods based on the measurement of the deformation induced by the cells on elastic substrate on which they are moving. Amoeboid cells migrate by implementing a motility cycle based on the sequential repetition of four phases. In this paper, we review the role that specific cytoskeletal components play in the regulation of the cell migration mechanics. We investigate the role of specific cytoskeletal components regarding the ability of the cells to perform the motility cycle effectively and the generation of traction forces. The actin nucleation in the leading edge of the cell, carried by the ARP2/3 complex activated through the SCAR/WAVE complex, has shown to be fundamental to the execution of the cyclic movement and to the generation of the traction forces. The protein PIR121, a member of the SCAR/WAVE complex, is essential to the proper regulation of the periodic movement and the protein SCAR, also included in the SCAR/WAVE complex, is necessary for the generation of the traction forces during migration. The protein Myosin II, an important F-actin cross-linker and motor protein, is essential to cytoskeletal contractility and to the generation and proper organization of the traction forces during migration.

scholarly journals Correlation of cellular traction forces and dissociation kinetics of adhesive protein zyxin revealed by multi-parametric live cell microscopy

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251411
Author(s):  
Lorena Sigaut ◽  
Micaela Bianchi ◽  
Catalina von Bilderling ◽  
Lía Isabel Pietrasanta
Keyword(s):  
Extracellular Matrix ◽  
Residence Time ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Traction Force ◽  
Correlation Spectroscopy ◽  
Substrate Stiffness ◽  
Dissociation Kinetics ◽  
Traction Forces ◽  
Cellular Division

Cells exert traction forces on the extracellular matrix to which they are adhered through the formation of focal adhesions. Spatial-temporal regulation of traction forces is crucial in cell adhesion, migration, cellular division, and remodeling of the extracellular matrix. By cultivating cells on polyacrylamide hydrogels of different stiffness we were able to investigate the effects of substrate stiffness on the generation of cellular traction forces by Traction Force Microscopy (TFM), and characterize the molecular dynamics of the focal adhesion protein zyxin by Fluorescence Correlation Spectroscopy (FCS) and Fluorescence Recovery After Photobleaching (FRAP). As the rigidity of the substrate increases, we observed an increment of both, cellular traction generation and zyxin residence time at the focal adhesions, while its diffusion would not be altered. Moreover, we found a positive correlation between the traction forces exerted by cells and the residence time of zyxin at the substrate elasticities studied. We found that this correlation persists at the subcellular level, even if there is no variation in substrate stiffness, revealing that focal adhesions that exert greater traction present longer residence time for zyxin, i.e., zyxin protein has less probability to dissociate from the focal adhesion.

Spatial and temporal dynamics of lexico-semantic processing in American Sign Language

2011 ◽  
Author(s):  
M. Leonard ◽  
N. Ferjan Ramirez ◽  
C. Torres ◽  
M. Hatrak ◽  
R. Mayberry ◽  
...  
Keyword(s):  
American Sign Language ◽  
Sign Language ◽  
Semantic Processing ◽  
Temporal Dynamics ◽  
American Sign ◽  
Spatial And Temporal Dynamics

Spatial and temporal dynamics of Pacific capelin Mallotus catervarius in the Gulf of Alaska: implications for ecosystem-based fisheries management

2020 ◽  
Vol 637 ◽  
pp. 117-140 ◽  
Author(s):  
DW McGowan ◽  
ED Goldstein ◽  
ML Arimitsu ◽  
AL Deary ◽  
O Ormseth ◽  
...  
Keyword(s):  
Temporal Dynamics ◽  
Marine Ecosystem ◽  
Gulf Of Alaska ◽  
Data Series ◽  
Limited Information ◽  
Important Species ◽  
Multiple Data ◽  
Spatial And Temporal Dynamics ◽  
Spawning Areas ◽  
Spatio Temporal

Pacific capelin Mallotus catervarius are planktivorous small pelagic fish that serve an intermediate trophic role in marine food webs. Due to the lack of a directed fishery or monitoring of capelin in the Northeast Pacific, limited information is available on their distribution and abundance, and how spatio-temporal fluctuations in capelin density affect their availability as prey. To provide information on life history, spatial patterns, and population dynamics of capelin in the Gulf of Alaska (GOA), we modeled distributions of spawning habitat and larval dispersal, and synthesized spatially indexed data from multiple independent sources from 1996 to 2016. Potential capelin spawning areas were broadly distributed across the GOA. Models of larval drift show the GOA’s advective circulation patterns disperse capelin larvae over the continental shelf and upper slope, indicating potential connections between spawning areas and observed offshore distributions that are influenced by the location and timing of spawning. Spatial overlap in composite distributions of larval and age-1+ fish was used to identify core areas where capelin consistently occur and concentrate. Capelin primarily occupy shelf waters near the Kodiak Archipelago, and are patchily distributed across the GOA shelf and inshore waters. Interannual variations in abundance along with spatio-temporal differences in density indicate that the availability of capelin to predators and monitoring surveys is highly variable in the GOA. We demonstrate that the limitations of individual data series can be compensated for by integrating multiple data sources to monitor fluctuations in distributions and abundance trends of an ecologically important species across a large marine ecosystem.

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