scholarly journals The interplay between matrix deformation and the coordination of turning events governs directed neutrophil migration in 3D matrices

2021 ◽  
Vol 7 (29) ◽  
pp. eabf3882
Author(s):  
Joshua François ◽  
Adithan Kandasamy ◽  
Yi-Ting Yeh ◽  
Amy Schwartz ◽  
Cindy Ayala ◽  
...  

Neutrophils migrating through extravascular spaces must negotiate narrow matrix pores without losing directional movement. We investigated how chemotaxing neutrophils probe matrices and adjust their migration to collagen concentration ([col]) changes by tracking 20,000 cell trajectories and quantifying cell-generated 3D matrix deformations. In low-[col] matrices, neutrophils exerted large deformations and followed straight trajectories. As [col] increased, matrix deformations decreased, and neutrophils turned often to circumvent rather than remodel matrix pores. Inhibiting protrusive or contractile forces shifted this transition to lower [col], implying that mechanics play a crucial role in defining migratory strategies. To balance frequent turning and directional bias, neutrophils used matrix obstacles as pivoting points to steer toward the chemoattractant. The Actin Related Protein 2/3 complex coordinated successive turns, thus controlling deviations from chemotactic paths. These results offer an improved understanding of the mechanisms and molecular regulators used by neutrophils during chemotaxis in restrictive 3D environments.

2020 ◽  
Author(s):  
Joshua François ◽  
Adithan Kandasamy ◽  
Yi-Ting Yeh ◽  
Cindy Ayala ◽  
Ruedi Meili ◽  
...  

AbstractThree-dimensional (3-D) neutrophil migration is essential for immune surveillance and inflammatory responses. During 3-D migration, especially through extravascular spaces, neutrophils rely on frontal protrusions and rear contractions to squeeze and maneuver through extracellular matrices containing narrow pores. However, the role of matrix density and the cells’ ability to probe and remodel matrix pores during 3-D chemotaxis are far from being understood. We investigated these processes by tracking the trajectories of over 20,000 neutrophils in a 3-D migration device containing collagen matrices of varying concentrations and analyzing the shape of these trajectories at multiple scales. Additionally, we quantified the transient 3-D matrix deformations caused by the migrating cells. The mean pore size of our reconstituted collagen matrices decreased when the collagen concentration ([col]) was increased. In low-[col] matrices, neutrophils exerted large transient deformations and migrated in relatively straight trajectories. In contrast, they were not able to appreciably deform high- [col] matrices and adapted to this inability by turning more often to circumvent these narrow matrix pores. While this adaptation resulted in slower migration, the cells were able to balance the more frequent turning with the long-range directional bias necessary for chemotaxis. Based on our statistical analysis of cell trajectories, we postulate that neutrophils achieve this balance by using matrix obstacles as pivoting points to steer their motion towards the chemoattractant. Inhibiting myosin-II contractility or Arp2/3-mediated pseudopod protrusions not only compromised the cells’ ability to deform the matrix, but also made them switch to increased turning in more restrictive matrices when compared to untreated control cells. Both myosin-II contractility and Arp2/3-mediated branched polymerization of actin played a role in fast migration, but Arp2/3 was also crucial for neutrophils when coordinating the orientations of successive turns to prevent veering away from the chemotactic path. These results may contribute to an improved understanding of the mechanisms employed by migrating neutrophils in confined 3-D environments, as well as the molecular and environmental regulators for maintaining persistent motion.


2015 ◽  
Vol 211 (3) ◽  
pp. 683-701 ◽  
Author(s):  
Charlotte Guetta-Terrier ◽  
Pascale Monzo ◽  
Jie Zhu ◽  
Hongyan Long ◽  
Lakshmi Venkatraman ◽  
...  

In vivo, cells migrate on complex three-dimensional (3D) fibrous matrices, which has made investigation of the key molecular and physical mechanisms that drive cell migration difficult. Using reductionist approaches based on 3D electrospun fibers, we report for various cell types that single-cell migration along fibronectin-coated nanofibers is associated with lateral actin-based waves. These cyclical waves have a fin-like shape and propagate up to several hundred micrometers from the cell body, extending the leading edge and promoting highly persistent directional movement. Cells generate these waves through balanced activation of the Rac1/N-WASP/Arp2/3 and Rho/formins pathways. The waves originate from one major adhesion site at leading end of the cell body, which is linked through actomyosin contractility to another site at the back of the cell, allowing force generation, matrix deformation and cell translocation. By combining experimental and modeling data, we demonstrate that cell migration in a fibrous environment requires the formation and propagation of dynamic, actin based fin-like protrusions.


2014 ◽  
Vol 205 (2) ◽  
pp. 155-162 ◽  
Author(s):  
Ayelet Lesman ◽  
Jacob Notbohm ◽  
David A. Tirrell ◽  
Guruswami Ravichandran

Physical forces direct the orientation of the cell division axis for cells cultured on rigid, two-dimensional (2D) substrates. The extent to which physical forces regulate cell division in three-dimensional (3D) environments is not known. Here, we combine live-cell imaging with digital volume correlation to map 3D matrix displacements and identify sites at which cells apply contractile force to the matrix as they divide. Dividing cells embedded in fibrous matrices remained anchored to the matrix by long, thin protrusions. During cell rounding, the cells released adhesive contacts near the cell body while applying tensile forces at the tips of the protrusions to direct the orientation of the cell division axis. After cytokinesis, the daughter cells respread into matrix voids and invaded the matrix while maintaining traction forces at the tips of persistent and newly formed protrusions. Mechanical interactions between cells and the extracellular matrix constitute an important mechanism for regulation of cell division in 3D environments.


Blood ◽  
2018 ◽  
Vol 131 (17) ◽  
pp. 1887-1898 ◽  
Author(s):  
Melanie Salvermoser ◽  
Robert Pick ◽  
Ludwig T. Weckbach ◽  
Annette Zehrer ◽  
Phillip Löhr ◽  
...  

Key Points Myo1f is critical for migration in 3D environments. Myo1f regulates the dynamic deformation of the nucleus during migration through physical barriers.


Author(s):  
J. Roemer ◽  
S.R. Simon

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.


1997 ◽  
Vol 40 (2) ◽  
pp. 400-404 ◽  
Author(s):  
Virginia A. Hinton ◽  
Winston M. C. Arokiasamy

It has been hypothesized that typical speech movements do not involve large muscular forces and that normal speakers use less than 20% of the maximum orofacial muscle contractile forces that are available (e.g., Amerman, 1993; Barlow & Abbs, 1984; Barlow & Netsell, 1986; DePaul & Brooks, 1993). However, no direct evidence for this hypothesis has been provided. This study investigated the percentage of maximum interlabial contact pressures (force per unit area) typically used during speech production. The primary conclusion of this study is that normal speakers typically use less than 20% of the available interlabial contact pressure, whether or not the jaw contributes to bilabial closure. Production of the phone [p] at conversational rate and intensity generated an average of 10.56% of maximum available interlabial pressure (MILP) when jaw movement was not restricted and 14.62% when jaw movement was eliminated.


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