Integrated computational and experimental pipeline for quantifying local cell–matrix interactions

AbstractCellular interactions with the extracellular matrix (ECM) play a key role in modulating biological processes. While studies have identified key molecular factors of these interactions, the mechanical regulation associated with these interactions is not well characterized. To address this, we present an image analysis platform to analyze time-dependent dynamics observed in lung fibroblasts embedded in a 3D collagen matrix. Combining drug studies with quantitative analysis of cell–matrix interactions, our results are able to provide cellular level quantitative insights for mechanical and biophysical phenomena relevant to cell-ECM interactions. This system overall represents an initial pipeline for understanding cell mechanics in a 3D collagen gel and their implications in a physiologically relevant context.

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Cell–Matrix Entanglement and Mechanical Anchorage of Fibroblasts in Three-dimensional Collagen Matrices

Molecular Biology of the Cell ◽

10.1091/mbc.e05-01-0007 ◽

2005 ◽

Vol 16 (11) ◽

pp. 5070-5076 ◽

Cited By ~ 69

Author(s):

Hongmei Jiang ◽

Frederick Grinnell

Keyword(s):

Tight Binding ◽

Three Dimensional ◽

Collagen Matrix ◽

Phagocytic Cells ◽

Collagen Matrices ◽

Cell Matrix ◽

Matrix Interactions ◽

The Matrix ◽

3D Collagen ◽

Cell Matrix Interactions

Fibroblast-3D collagen matrix culture provides a physiologically relevant model to study cell–matrix interactions. In tissues, fibroblasts are phagocytic cells, and in culture, they have been shown to ingest both fibronectin and collagen-coated latex particles. Compared with cells on collagen-coated coverslips, phagocytosis of fibronectin-coated beads by fibroblasts in collagen matrices was found to be reduced. This decrease could not be explained by integrin reorganization, tight binding of fibronectin beads to the collagen matrix, or differences in overall bead binding to the cells. Rather, entanglement of cellular dendritic extensions with collagen fibrils seemed to interfere with the ability of the extensions to interact with the beads. Moreover, once these extensions became entangled in the matrix, cells developed an integrin-independent component of adhesion. We suggest that cell–matrix entanglement represents a novel mechanism of cell anchorage that uniquely depends on the three-dimensional character of the matrix.

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Imaging Cell-Matrix Interactions in 3D Collagen Hydrogel Culture Systems

Macromolecular Bioscience ◽

10.1002/mabi.201600478 ◽

2017 ◽

Vol 17 (6) ◽

pp. 1600478 ◽

Cited By ~ 7

Author(s):

Aaron R. Short ◽

Catherine Czeisler ◽

Benjamin Stocker ◽

Sara Cole ◽

José Javier Otero ◽

...

Keyword(s):

Culture Systems ◽

Collagen Hydrogel ◽

Cell Matrix ◽

Matrix Interactions ◽

3D Collagen ◽

Cell Matrix Interactions

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Modulation of Fibroblast Morphology and Adhesion during Collagen Matrix Remodeling

Molecular Biology of the Cell ◽

10.1091/mbc.e02-05-0291 ◽

2002 ◽

Vol 13 (11) ◽

pp. 3915-3929 ◽

Cited By ~ 168

Author(s):

Elisa Tamariz ◽

Frederick Grinnell

Keyword(s):

Wound Repair ◽

Three Dimensional ◽

Rho Kinase ◽

Focal Adhesions ◽

Collagen Matrix ◽

Collagen Fibrils ◽

Matrix Remodeling ◽

Cell Matrix ◽

Matrix Interactions ◽

Cell Matrix Interactions

When fibroblasts are placed within a three-dimensional collagen matrix, cell locomotion results in translocation of the flexible collagen fibrils of the matrix, a remodeling process that has been implicated in matrix morphogenesis during development and wound repair. In the current experiments, we studied formation and maturation of cell–matrix interactions under conditions in which we could distinguish local from global matrix remodeling. Local remodeling was measured by the movement of collagen-embedded beads towards the cells. Global remodeling was measured by matrix contraction. Our observations show that no direct relationship occurs between protrusion and retraction of cell extensions and collagen matrix remodeling. As fibroblasts globally remodel the collagen matrix, however, their overall morphology changes from dendritic to stellate/bipolar, and cell–matrix interactions mature from punctate to focal adhesion organization. The less well organized sites of cell–matrix interaction are sufficient for translocating collagen fibrils, and focal adhesions only form after a high degree of global remodeling occurs in the presence of growth factors. Rho kinase activity is required for maturation of fibroblast morphology and formation of focal adhesions but not for translocation of collagen fibrils.

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Use of F9 teratocarcinoma STEM cells to study cell-matrix interactions in the early mouse embryo

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123416 ◽

1992 ◽

Vol 50 (1) ◽

pp. 602-603

Author(s):

Marc Lenburg ◽

Rulang Jiang ◽

Lengya Cheng ◽

Laura Grabel

Keyword(s):

Mouse Embryo ◽

Inner Cell Mass ◽

Cell Mass ◽

Cell Types ◽

Embryoid Bodies ◽

F9 Cells ◽

Cell Matrix ◽

Matrix Interactions ◽

Cell Matrix Interactions ◽

F9 Teratocarcinoma

We are interested in defining the cell-cell and cell-matrix interactions that help direct the differentiation of extraembryonic endoderm in the peri-implantation mouse embryo. At the blastocyst stage the mouse embryo consists of an outer layer of trophectoderm surrounding the fluid-filled blastocoel cavity and an eccentrically located inner cell mass. On the free surface of the inner cell mass, facing the blastocoel cavity, a layer of primitive endoderm forms. Primitive endoderm then generates two distinct cell types; parietal endoderm (PE) which migrates along the inner surface of the trophectoderm and secretes large amounts of basement membrane components as well as tissue-type plasminogen activator (tPA), and visceral endoderm (VE), a columnar epithelial layer characterized by tight junctions, microvilli, and the synthesis and secretion of α-fetoprotein. As these events occur after implantation, we have turned to the F9 teratocarcinoma system as an in vitro model for examining the differentiation of these cell types. When F9 cells are treated in monolayer with retinoic acid plus cyclic-AMP, they differentiate into PE. In contrast, when F9 cells are treated in suspension with retinoic acid, they form embryoid bodies (EBs) which consist of an outer layer of VE and an inner core of undifferentiated stem cells. In addition, we have established that when VE containing embryoid bodies are plated on a fibronectin coated substrate, PE migrates onto the matrix and this interaction is inhibited by RGDS as well as antibodies directed against the β1 integrin subunit. This transition is accompanied by a significant increase in the level of tPA in the PE cells. Thus, the outgrowth system provides a spatially appropriate model for studying the differentiation and migration of PE from a VE precursor.

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Cell matrix interactions in asthma

Clinical & Experimental Allergy ◽

10.1046/j.1365-2222.1997.d01-423.x ◽

1997 ◽

Vol 27 (1) ◽

pp. 22-27

Author(s):

K. GOLDRING ◽

J. A. WARNER

Keyword(s):

Cell Matrix ◽

Matrix Interactions ◽

Cell Matrix Interactions

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Cell-Matrix Interactions in Breast Carcinoma Invasion

10.21236/ada391446 ◽

2000 ◽

Author(s):

Anna M. Curatola

Keyword(s):

Breast Carcinoma ◽

Cell Matrix ◽

Matrix Interactions ◽

Cell Matrix Interactions

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A computational framework for modeling cell–matrix interactions in soft biological tissues

Biomechanics and Modeling in Mechanobiology ◽

10.1007/s10237-021-01480-2 ◽

2021 ◽

Author(s):

Jonas F. Eichinger ◽

Maximilian J. Grill ◽

Iman Davoodi Kermani ◽

Roland C. Aydin ◽

Wolfgang A. Wall ◽

...

Keyword(s):

Soft Tissues ◽

Three Dimensional ◽

Biological Tissues ◽

Computational Framework ◽

Cell Matrix ◽

Physiological Processes ◽

Matrix Interactions ◽

Mechanical Homeostasis ◽

Cell Matrix Interactions ◽

Short Time

AbstractLiving soft tissues appear to promote the development and maintenance of a preferred mechanical state within a defined tolerance around a so-called set point. This phenomenon is often referred to as mechanical homeostasis. In contradiction to the prominent role of mechanical homeostasis in various (patho)physiological processes, its underlying micromechanical mechanisms acting on the level of individual cells and fibers remain poorly understood, especially how these mechanisms on the microscale lead to what we macroscopically call mechanical homeostasis. Here, we present a novel computational framework based on the finite element method that is constructed bottom up, that is, it models key mechanobiological mechanisms such as actin cytoskeleton contraction and molecular clutch behavior of individual cells interacting with a reconstructed three-dimensional extracellular fiber matrix. The framework reproduces many experimental observations regarding mechanical homeostasis on short time scales (hours), in which the deposition and degradation of extracellular matrix can largely be neglected. This model can serve as a systematic tool for future in silico studies of the origin of the numerous still unexplained experimental observations about mechanical homeostasis.

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