scholarly journals Force-exerting lateral protrusions in fibroblastic cell contraction

2019 ◽  
Author(s):  
Abinash Padhi ◽  
Karanpreet Singh ◽  
Janusz Franco-Barraza ◽  
Daniel J. Marston ◽  
Edna Cukierman ◽  
...  

ABSTRACTAligned extracellular matrix fibers enable fibroblasts to undergo myofibroblastic activation and lead to elongated cell morphology. The fibroblasts in turn contract to cause alignment of the extracellular matrix. This feedback process is critical in pathological occurrences such as desmoplasia and is not well understood. Using engineered fiber networks that serve as force sensors, we identify lateral protrusions with specific functions and morphology that are induced by elongated fibroblastic cells and which apply extracellular fiber-deflecting contractile forces. Lateral projections, named twines, produce twine bridges upon interacting with neighboring parallel fibers. These mature into “perpendicular lateral protrusions” (PLPs) that enable cells to spread laterally and effectively contract. Using quantitative microscopy, we show that the twines originate from the stratification of cyclic actin waves traversing the entire length of the cell. The primary twines swing freely in 3D and engage neighboring extracellular fibers. Once engaged, a lamellum extends from the primary twine and forms a second twine, which also engages with the neighboring fiber. As the lamellum fills in the space between the two twines, a sheet-like PLP is formed to contract effectively. By controlling the geometry of extracellular networks we confirm that anisotropic fibrous environments enable PLP formation, and these force-generating PLPs are oriented perpendicular to the parent cell body. PLP formation kinetics indicated mechanisms analogous to other/known actin-based structures. Our identification of force-exerting PLPs in anisotropic fibrous environments suggests an explanation for cancer-associated desmoplastic expansion at single-cell resolution, providing possible new clinical intervention opportunities.

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Abinash Padhi ◽  
Karanpreet Singh ◽  
Janusz Franco-Barraza ◽  
Daniel J. Marston ◽  
Edna Cukierman ◽  
...  

AbstractAligned extracellular matrix fibers enable fibroblasts to undergo myofibroblastic activation and achieve elongated shapes. Activated fibroblasts are able to contract, perpetuating the alignment of these fibers. This poorly understood feedback process is critical in chronic fibrosis conditions, including cancer. Here, using fiber networks that serve as force sensors, we identify “3D perpendicular lateral protrusions” (3D-PLPs) that evolve from lateral cell extensions named twines. Twines originate from stratification of cyclic-actin waves traversing the cell and swing freely in 3D to engage neighboring fibers. Once engaged, a lamellum forms and extends multiple secondary twines, which fill in to form a sheet-like PLP, in a force-entailing process that transitions focal adhesions to activated (i.e., pathological) 3D-adhesions. The specific morphology of PLPs enables cells to increase contractility and force on parallel fibers. Controlling geometry of extracellular networks confirms that anisotropic fibrous environments support 3D-PLP formation and function, suggesting an explanation for cancer-associated desmoplastic expansion.


1981 ◽  
Vol 88 (2) ◽  
pp. 294-300 ◽  
Author(s):  
K S Steimer ◽  
M Klagsbrun

Bovine milk may be used as a supplement for the serum-free growth of certain fibroblastic cells in culture. The growth properties of three representative cell types in milk-supplemented medium were examined; fibroblastic cell strains, fibroblastic cell lines, and transformed fibroblasts. Transformed fibroblasts, which included RNA and DNA tumor virus-transformed cells and carcinogen-transformed cells, grew in milk. Instead of growing attached to the culture dishes, as they normally do in serum, transformed fibroblasts grew in milk as large clusters in suspension. In contrast, nontransformed fibroblastic cell strains and cell lines did not grow in milk-supplemented medium. Fibroblasts transformed by a temperature-sensitive transformation mutant of Rous sarcoma virus were temperature-sensitive for growth in milk. The failure of cells to adhere to the substratum in milk-supplemented medium suggested that milk might be deficient in attachment factors for fibroblasts. When the attachment of fibroblastic cells in milk-supplemented medium was facilitated by pretreating culture dishes with fibronectin, (a) transformed cells grew attached rather than in suspension, (b) normal cell lines attached and grew to confluence, and (c) normal cell strains adhered and survived but did not exhibit appreciable cell proliferation.


In Vitro ◽  
1983 ◽  
Vol 19 (2) ◽  
pp. 127-133 ◽  
Author(s):  
M. A. Riederer-Henderson ◽  
A. Gauger ◽  
L. Olson ◽  
C. Robertson ◽  
T. K. Greenlee

1969 ◽  
Vol 15 (3) ◽  
pp. 273-277 ◽  
Author(s):  
Sunidhkumar S. Gandhi ◽  
Robert B. Stewart

Cultures of fibroblastic cells prepared from chick embryo lung infected with low multiplicities of influenza type A virus strains were found to produce more interferon than did cultures of epithelial cells prepared from the same organ. Fibroblastic cell cultures were also found to be more sensitive to the action of interferon than were epithelial cells with respect to the levels of infectious virus produced and the duration of interferon action. Cultures of the two cell types treated with interferon did not differ with respect to the number of cells involved in virus synthesis.


2017 ◽  
Author(s):  
Andrea Malandrino ◽  
Michael Mak ◽  
Xavier Trepat ◽  
Roger D. Kamm

AbstractThe mechanical properties of the extracellular matrix (ECM) – a complex, 3D, fibrillar scaffold of cells in physiological environments – modulate cell behavior and can drive tissue morphogenesis, regeneration, and disease progression. For simplicity, it is often convenient to assume these properties to be time-invariant. In living systems, however, cells dynamically remodel the ECM and create time-dependent local environments. Here, we demonstrate that cell generated contractile forces are capable of producing substantial irreversible changes to the density and architecture of physiologically relevant ECMs – collagen I and fibrin – in a matter of minutes. We measure the 3D mechanical deformation profiles of the ECM surrounding cancer and endothelial cells during stages when force generation is active or inactive. We further correlate these measurements to both discrete fiber simulations that incorporate fiber crosslink unbinding kinetics and continuum-scale modeling. Our findings reveal that plasticity, as a mechanical law in these networks, is fundamentally related to the force-driven unbinding of fiber crosslinks. These results illustrate the dynamic nature of the mechanical environment of physiologically mimicking cell-in-gel systems.


1985 ◽  
Vol 79 (1) ◽  
pp. 83-94 ◽  
Author(s):  
H. Harris

When malignant cells, defined by their ability to grow progressively in genetically compatible hosts, are fused with diploid fibroblasts of the same species, the resulting hybrid cells, so long as they retain certain specific chromosomes donated by the diploid parent cell, are non-malignant. When these particular chromosomes are eliminated from the hybrid, the malignant phenotype reappears, and the segregant cell is again able to grow progressively in vivo. In the present experiments the histological character of the lesions produced by the inoculation of crosses between malignant and non-malignant cells was examined. It was found, in a wide range of material, and without exception, that where one or other of the parent cells in the cross was of fibroblastic lineage, malignancy was suppressed when the hybrid cells produced a collagenous extracellular matrix in vivo; and it reappeared when genetic segregants were produced that had lost the ability to produce this matrix. These results are interpreted in terms of a general model in which it is proposed that the progressive multiplication of malignant cells in vivo is a secondary consequence of a genetically stable impairment of terminal differentiation.


Soft Matter ◽  
2021 ◽  
Author(s):  
Brandon Matthew Slater ◽  
Jing Li ◽  
Dhiraj Indana ◽  
Yihao Xie ◽  
Ovijit Chaudhuri ◽  
...  

During various physiological processes, such as wound healing and cell migration, cells continuously interact mechanically with a surrounding extracellular matrix (ECM). Contractile forces generated by the actin cytoskeleton are transmitted...


2021 ◽  
Author(s):  
Redaet Daniel ◽  
Patricia Bilodeau ◽  
Abebech Mengeta ◽  
Kimmy Yang ◽  
Jonathan M. Lee

Abstract Focal Adhesions (FA) couple the actin cytoskeleton to the extracellular matrix through transmembrane integrin receptors. FA assembly and disassembly regulate cell migration by controlling substrate interaction and the generation of intracellular contractile forces. Here we show that FA interact with mitochondria. Mitochondria are highly dynamic organelles that are now emerging as regulators of mammalian cell motility. We find that mitochondria infiltrate the leading edge of NIH3T3 fibroblasts during migration and tether to FA there. Importantly, we find that FA interacting with mitochondria are larger than those lacking mitochondrial interaction. In addition, inhibition of mitochondrial ATP generation reduces FA size and artificial tethering of FA to mitochondria concomitantly increases their size. Taken together this suggests that mitochondrial interaction with FA is a functional part of cell migration and adhesion.


2014 ◽  
Vol 64 (4) ◽  
pp. 397-412 ◽  
Author(s):  
Kukolj Vladimir

Abstract Myofibroblasts, cells sharing characteristics with fibroblasts and smooth muscle cells, may have a very heterogeneous origin. The myofibroblasts may be derived from a variety of sources including resident mesenchymal cells, epithelial to mesenchymal transition, as well as from circulating fibroblast-like cells called fibrocytes that are derived from bone-marrow stem cells, or derived from bone marrow precursors. In normal conditions, fibroblastic cells exhibit a low extracellular matrix production ability. After tissue injury, they become activated by cytokines locally released from inflammatory and resident cells to migrate into the damaged tissue and to synthesize extracellular matrix components. The investigation of cytoskeletal and cell surface markers showed a certain degree of heterogeneity of these cells. The reason for this is that markers these cells express to a large extent depend on the type of animal, age and stage of development of fibrosis. A better knowledge of the molecular mechanisms involved in the appearance of differentiated myofibroblasts in different pathological situations will be useful for understanding the development of fibrosis, its prevention and therapy


Sign in / Sign up

Export Citation Format

Share Document