Guiding cell migration in 3D: A collagen matrix with graded directional stiffness

2009 ◽  
Vol 66 (3) ◽  
pp. 121-128 ◽  
Author(s):  
Ektoras Hadjipanayi ◽  
Vivek Mudera ◽  
Robert A. Brown
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kaoru Miyazaki ◽  
Jun Oyanagi ◽  
Daisuke Hoshino ◽  
Shinsaku Togo ◽  
Hiromichi Kumagai ◽  
...  

1999 ◽  
Vol 146 (5) ◽  
pp. 1107-1116 ◽  
Author(s):  
David A. Cheresh ◽  
Jie Leng ◽  
Richard L. Klemke

Cell migration and wound contraction requires assembly of actin into a functional myosin motor unit capable of generating force. However, cell migration also involves formation of actin-containing membrane ruffles. Evidence is provided that actin-myosin assembly and membrane ruffling are regulated by distinct signaling pathways in the migratory cell. Interaction of cells with extracellular matrix proteins or cytokines promote cell migration through activation of the MAP kinases ERK1 and ERK2 as well as the molecular coupling of the adaptor proteins p130CAS and c-CrkII. ERK signaling is independent of CAS/Crk coupling and regulates myosin light chain phosphorylation leading to actin-myosin assembly during cell migration and cell-mediated contraction of a collagen matrix. In contrast, membrane ruffling, but not cell contraction, requires Rac GTPase activity and the formation of a CAS/Crk complex that functions in the context of the Rac activating protein DOCK180. Thus, during cell migration ERK and CAS/Crk coupling operate as components of distinct signaling pathways that control actin assembly into myosin motors and membrane ruffles, respectively.


2016 ◽  
Vol 11 (4) ◽  
pp. 316-326 ◽  
Author(s):  
Aline Appert-Collin ◽  
Amar Bennasroune ◽  
Pierre Jeannesson ◽  
Christine Terryn ◽  
Guy Fuhrmann ◽  
...  

2020 ◽  
Vol 318 (2) ◽  
pp. L276-L286 ◽  
Author(s):  
Marisa Tisler ◽  
Samuel Alkmin ◽  
Hsin-Yu Chang ◽  
Jon Leet ◽  
Ksenija Bernau ◽  
...  

Idiopathic pulmonary fibrosis (IPF) is characterized by a profound remodeling of the collagen in the extracellular matrix (ECM), where the fibers become both denser and more highly aligned. However, it is unknown how this reconfiguration of the collagen matrix affects disease progression. Here, we investigate the role of specific alterations in collagen fiber organization on cell migration dynamics by using biomimetic image-based collagen scaffolds representing normal and fibrotic lung, where the designs are derived directly from high-resolution second harmonic generation microscopy images. The scaffolds are fabricated by multiphoton-excited (MPE) polymerization, where the process is akin to three-dimensional printing, except that it is performed at much greater resolution (∼0.5 microns) and with collagen and collagen analogs. These scaffolds were seeded with early passaged primary human normal and IPF fibroblasts to enable the decoupling of the effect of cell-intrinsic characteristics (normal vs. IPF) versus ECM structure (normal vs. IPF) on migration dynamics. We found that the highly aligned IPF collagen structure promoted enhanced cell elongation and F-actin alignment along with increased cell migration speed and straightness relative to the normal tissues. Collectively, the data are consistent with an enhanced contact guidance mechanism on the aligned IPF matrix. Although cell intrinsic effects were observed, the aligned collagen matrix morphology had a larger effect on these metrics. Importantly, these biomimetic models of the lung cannot be synthesized by conventional fabrication methods. We suggest that the MPE image-based fabrication method will enable additional hypothesis-based testing studies of cell-matrix interactions in the context of tissue fibrosis.


Author(s):  
Nadine Rommerswinkel ◽  
Bernd Niggemann ◽  
Silvia Keil ◽  
Kurt S. Zänker ◽  
Thomas Dittmar

1991 ◽  
Vol 2 (8) ◽  
pp. 613-625 ◽  
Author(s):  
K Turksen ◽  
Y Choi ◽  
E Fuchs

When cultured on plastic and treated with transforming growth factor alpha (TGF alpha), human keratinocytes exhibit an increase in proliferation at the colony periphery, apparently as a consequence of enhanced cell migration (Barrandon and Green, 1987). To investigate the effects of TGF alpha on a differentiating stratified squamous epithelium and to begin to examine the molecular basis mediating this influence, we cultured human epidermal cells on a gelled lattice of collagen and fibroblasts, floating on the air-liquid interface. Under these conditions, raft cultures differentiate and exhibit morphological and biochemical features of human skin in vivo (Asselineau et al., 1986; Kopan et al., 1987). When 3-wk-old raft cultures were treated with TGF alpha, basal cells showed a marked increase in cell proliferation. At elevated concentrations of TGF alpha, the organization of cells within the artificial tissue changed and islands of basal cells entered the collagen matrix. Biochemical analysis of the response revealed that type I collagenase and gelatinase were induced by keratinocytes within 12 h after TGF alpha treatment. In contrast, invasion of basal cells into the collagen matrix was not significant until 48-72 h post-treatment, suggesting that collagenase and gelatinase production may be a prerequisite to this phenomenon. These results have important implications for the possible role of TGF alpha in squamous cell carcinoma and tumor invasion.


10.1114/1.227 ◽  
1999 ◽  
Vol 27 (6) ◽  
pp. 721-730 ◽  
Author(s):  
Partha Roy ◽  
W. M. Petroll ◽  
C. J. Chuong ◽  
H. D. Cavanagh ◽  
J. V. Jester

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