Research article summary (published 4 Mar 2007):

A new microrheometric approach reveals individual and cooperative roles for TGF-beta1 and IL-1beta in fibroblast-mediated stiffening of collagen gels.

Full Abstract

The stiffness of the extracellular matrix can profoundly influence cell and tissue behaviors. Thus there is an emerging emphasis on understanding how matrix mechanical environments are established, regulated, and modified. Here we develop a microrheometric assay to measure the mechanical properties of a model extracellular matrix (type I collagen gel) and use it to explore cytokine-induced, cell-mediated changes in matrix mechanical properties. The microrheometric assay uses micron-scale ferrimagnetic beads embedded within collagen gels during fibrillogenesis. The beads are magnetized, then subjected to a twisting field, with the aggregate rotation of the beads measured by a magnetometer. The degree of bead rotation reflects the stiffness of the surrounding matrix. We show that the microscale assay provides stiffness measures for collagen gels comparable to those obtained with standard macroscale rheometry. To demonstrate the utility of the assay for biological discovery, we measure stiffness changes in fibroblast-populated collagen gels exposed to three concentrations of six cytokines over 2 to 14 days. Among the cytokines tested, transforming growth factor-beta1 and interleukin-1beta enhanced matrix stiffness, and together exerted cooperative effects on cellular modulation of matrix mechanics. The microrheometry approach developed here should accelerate the discovery of biological pathways orchestrating cellular modulation of matrix mechanics.

Author information

Author/s: Leung, Lester Y (LY); Tian, David (D); Brangwynne, Clifford P (CP); Weitz, David A (DA); Tschumperlin, Daniel J (DJ);

Affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

Grants: GM73628 (Agency:NIGMS NIH HHS) ; HL33009 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J), published in United States. (Language: eng)

Reference: 2007-Jul; vol 21 (issue 9) : pp 2064-73

Dates: Created 2007/06/26; Completed 2007/08/15; Revised 2008/11/21;

PMID: 17341683, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Actins - biosynthesis; genetics Cells, Cultured Collagen - chemistry Collagen Type I - biosynthesis; genetics Collagen Type III - biosynthesis; genetics Computer Systems Connective Tissue Growth Factor Cytokines - pharmacology Drug Synergism Elasticity Extracellular Matrix Fibroblasts - physiology Gels Gene Expression Regulation - drug effects Humans

Immediate-Early Proteins - biosynthesis; genetics Intercellular Signaling Peptides and Proteins - biosynthesis; genetics Interleukin-1beta - pharmacology; physiology Lung - cytology Magnetics Materials Testing - methods Microchemistry - methods Microspheres Platelet-Derived Growth Factor - pharmacology; physiology Polymerase Chain Reaction Recombinant Proteins - pharmacology Rheology - methods Rotation Torque Transforming Growth Factor beta1 - pharmacology; physiology

Associated Chemicals: Actins (0) ; CTGF protein, human (0) ; Collagen Type I (0) ; Collagen Type III (0) ; Cytokines (0) ; Gels (0) ; Immediate-Early Proteins (0) ; Intercellular Signaling Peptides and Proteins (0) ; Interleukin-1beta (0) ; Platelet-Derived Growth Factor (0) ; Recombinant Proteins (0) ; Transforming Growth Factor beta1 (0) ; platelet-derived growth factor BB (0) ; Connective Tissue Growth Factor (139568-91-5) ; Collagen (9007-34-5)

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