scholarly journals Crowding tunes 3D collagen fibrils and reveals matrix regulation of cancer cell morphogenesis

2018 ◽  
Author(s):  
A. Han ◽  
S. Ranamukhaarachchi ◽  
D. O. Velez ◽  
A. Kumar ◽  
A. J. Engler ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Collagen Fibril ◽  
Cell Shape ◽  
Cell Phenotype ◽  
Cell Morphogenesis ◽  
Collagen Matrices ◽  
3D Collagen ◽  
Collagen Density ◽  
Underlying Mechanisms ◽  
Fibril Length

AbstractIt is well established that the collagenous extracellular matrix surrounding solid tumors significantly influences the dissemination of cancer cells. However, the underlying mechanisms remain poorly understood, in part because of a lack of methods to modulate collagen fibril topology in the presence of embedded cells. In this work, we develop a technique to tune the fibril architecture of cell-laden 3D collagen matrices using PEG as an inert molecular crowding agent. With this approach, we demonstrate that fibril length and pore size can be modulated independently of bulk collagen density and stiffness. Using live cell imaging and quantitative analysis, we show that matrices with long fibrils induce cell elongation and single cell migration, while shorter fibrils induce cell rounding, collective migration, and morphogenesis. We conclude that fibril architecture is an independent regulator of cancer cell phenotype and that cell shape and invasion strategy are functions of collagen fibril length.

Cell morphogenesis of trichomes in Arabidopsis: differential control of primary and secondary branching by branch initiation regulators and cell growth

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3779-3786 ◽  
Author(s):  
U. Folkers ◽  
J. Berger ◽  
M. Hulskamp
Keyword(s):  
Cell Growth ◽  
Cell Shape ◽  
Normal Development ◽  
Branching Pattern ◽  
Cell Morphogenesis ◽  
Negative Regulators ◽  
Branch Number ◽  
Underlying Mechanisms ◽  
Differential Control ◽  
Trichome Cell

Cell morphogenesis, i.e. the acquisition of a particular cell shape, can be examined genetically in the three-branched trichomes that differentiate from single epidermal cells on the leaves of Arabidopsis thaliana. In normal development, the growing trichome cell undergoes two successive branching events, resulting in a proximal side stem and a distal main stem which subsequently splits in two branches. Using new and previously described trichome mutants, we have analyzed the branching pattern in single and double mutants affecting branch number or cell size in order to determine underlying mechanisms. Our results suggest that primary branching is genetically distinct from subsequent branching events and that the latter, secondary events are initiated in response to positive and negative regulators of branching as well as subject to control by cell growth. We propose a model of how trichome cell morphogenesis is regulated during normal development.

scholarly journals LRP-1 Promotes Colon Cancer Cell Proliferation in 3D Collagen Matrices by Mediating DDR1 Endocytosis

2020 ◽  
Vol 8 ◽  
Author(s):  
Cao Cuong Le ◽  
Amar Bennasroune ◽  
Guillaume Collin ◽  
Cathy Hachet ◽  
Véronique Lehrter ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Collagen Matrices ◽  
3D Collagen

scholarly journals Inhomogeneities in 3D Collagen Matrices Impact Matrix Mechanics and Cancer Cell Migration

2020 ◽  
Vol 8 ◽  
Author(s):  
Alexander Hayn ◽  
Tony Fischer ◽  
Claudia Tanja Mierke
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Cancer Cell Migration ◽  
Collagen Matrices ◽  
Matrix Mechanics ◽  
3D Collagen

scholarly journals Collagen Fibril Flow and Tissue Translocation Coupled to Fibroblast Migration in 3D Collagen Matrices

2008 ◽  
Vol 19 (5) ◽  
pp. 2051-2058 ◽  
Author(s):  
Miguel Miron-Mendoza ◽  
Joachim Seemann ◽  
Frederick Grinnell
Keyword(s):  
Cell Migration ◽  
Collagen Fibril ◽  
Large Scale ◽  
Human Fibroblasts ◽  
Time Lapse ◽  
Collagen Matrices ◽  
Fibroblast Migration ◽  
Tractional Force ◽  
3D Collagen ◽  
Dermal Equivalents

In nested collagen matrices, human fibroblasts migrate from cell-containing dermal equivalents into surrounding cell-free outer matrices. Time-lapse microscopy showed that in addition to cell migration, collagen fibril flow occurred in the outer matrix toward the interface with the dermal equivalent. Features of this flow suggested that it depends on the same cell motile machinery that normally results in cell migration. Collagen fibril flow was capable of producing large-scale tissue translocation as shown by closure of a ∼1-mm gap between paired dermal equivalents in floating, nested collagen matrices. Our findings demonstrate that when fibroblasts interact with collagen matrices, tractional force exerted by the cells can couple to matrix translocation as well as to cell migration.

scholarly journals Biomimetic 3D Models for Investigating the Role of Monocytes and Macrophages in Atherosclerosis

2020 ◽  
Vol 7 (3) ◽  
pp. 113 ◽  
Author(s):  
Anna Garcia-Sabaté ◽  
Walaa Kamal E. Mohamed ◽  
Jiranuwat Sapudom ◽  
Aseel Alatoom ◽  
Layla Al Safadi ◽  
...  
Keyword(s):  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
3D Models ◽  
Dependent Manner ◽  
Collagen Matrices ◽  
Monocytes And Macrophages ◽  
3D Collagen ◽  
Collagen Density

Atherosclerosis, the inflammation of artery walls due to the accumulation of lipids, is the most common underlying cause for cardiovascular diseases. Monocytes and macrophages are major cells that contribute to the initiation and progression of atherosclerotic plaques. During this process, an accumulation of LDL-laden macrophages (foam cells) and an alteration in the extracellular matrix (ECM) organization leads to a local vessel stiffening. Current in vitro models are carried out onto two-dimensional tissue culture plastic and cannot replicate the relevant microenvironments. To bridge the gap between in vitro and in vivo conditions, we utilized three-dimensional (3D) collagen matrices that allowed us to mimic the ECM stiffening during atherosclerosis by increasing collagen density. First, human monocytic THP-1 cells were embedded into 3D collagen matrices reconstituted at low and high density. Cells were subsequently differentiated into uncommitted macrophages (M0) and further activated into pro- (M1) and anti-inflammatory (M2) phenotypes. In order to mimic atherosclerotic conditions, cells were cultured in the presence of oxidized LDL (oxLDL) and analyzed in terms of oxLDL uptake capability and relevant receptors along with their cytokine secretomes. Although oxLDL uptake and larger lipid size could be observed in macrophages in a matrix dependent manner, monocytes showed higher numbers of oxLDL uptake cells. By analyzing major oxLDL uptake receptors, both monocytes and macrophages expressed lectin-like oxidized low-density lipoprotein receptor-1 (LOX1), while enhanced expression of scavenger receptor CD36 could be observed only in M2. Notably, by analyzing the secretome of macrophages exposed to oxLDL, we demonstrated that the cells could, in fact, secrete adipokines and growth factors in distinct patterns. Besides, oxLDL appeared to up-regulate MHCII expression in all cells, while an up-regulation of CD68, a pan-macrophage marker, was found only in monocytes, suggesting a possible differentiation of monocytes into a pro-inflammatory macrophage. Overall, our work demonstrated that collagen density in the plaque could be one of the major factors driving atherosclerotic progression via modulation of monocyte and macrophages behaviors.

scholarly journals 3D collagen fibrillar microstructure guides pancreatic cancer cell phenotype and serves as a critical design parameter for phenotypic models of EMT

PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0188870 ◽  
Author(s):  
T. J. Puls ◽  
Xiaohong Tan ◽  
Catherine F. Whittington ◽  
Sherry L. Voytik-Harbin
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cell ◽  
Design Parameter ◽  
Pancreatic Cancer Cell ◽  
Cell Phenotype ◽  
Critical Design ◽  
3D Collagen

scholarly journals Endothelial lumen signaling complexes control 3D matrix–specific tubulogenesis through interdependent Cdc42- and MT1-MMP–mediated events

Blood ◽  
2010 ◽  
Vol 115 (25) ◽  
pp. 5259-5269 ◽  
Author(s):  
Anastasia Sacharidou ◽  
Wonshill Koh ◽  
Amber N. Stratman ◽  
Anne M. Mayo ◽  
Kevin E. Fisher ◽  
...  
Keyword(s):  
Tube Formation ◽  
Dominant Negative ◽  
Collagen Matrices ◽  
Signaling Complex ◽  
Vascular Morphogenesis ◽  
Cytoplasmic Tails ◽  
3D Matrix ◽  
Dependent Signal ◽  
3D Collagen ◽  
Membrane Type

Abstract Here, we define an endothelial cell (EC) lumen signaling complex involving Cdc42, Par6b, Par3, junction adhesion molecule (Jam)–B and Jam-C, membrane type 1–matrix metalloproteinase (MT1-MMP), and integrin α2β1, which coassociate to control human EC tubulogenesis in 3D collagen matrices. Blockade of both Jam-B and Jam-C using antibodies, siRNA, or dominant-negative mutants completely interferes with lumen and tube formation resulting from a lack of Cdc42 activation, inhibition of Cdc42-GTP–dependent signal transduction, and blockade of MT1-MMP–dependent proteolysis. This process requires interdependent Cdc42 and MT1-MMP signaling, which involves Par3 binding to the Jam-B and Jam-C cytoplasmic tails, an interaction that is necessary to physically couple the components of the lumen signaling complex. MT1-MMP proteolytic activity is necessary for Cdc42 activation during EC tube formation in 3D collagen matrices but not on 2D collagen surfaces, whereas Cdc42 activation is necessary for MT1-MMP to create vascular guidance tunnels and tube networks in 3D matrices through proteolytic events. This work reveals a novel interdependent role for Cdc42-dependent signaling and MT1-MMP–dependent proteolysis, a process that occurs selectively in 3D collagen matrices and that requires EC lumen signaling complexes, to control human EC tubulogenesis during vascular morphogenesis.

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