The extracellular matrix (ECM) is a complex web of secreted molecules that are assembled into diverse structures. In addition to providing cells with structural support and segregating them from cells in different tissues, the cellular sensing and relay of both chemical and mechanical cues from the ECM, through cell–matrix connections such as focal adhesions, influences cell morphology, movement and function, and even cell fate. Furthermore, the ECM is a highly dynamic structure that is constantly remodelled to control tissue homeostasis and development and it must be modified by tumour cells to allow invasion and metastasis. Thus, it is not surprising that the dysregulation of ECM structure, composition and function can lead to diseases such as fibrosis and cancer, which makes the ECM an attractive therapeutic target.
This specially commissioned Focus issue takes a look at the ECM at several levels, from its formation to its function, highlighting how our knowledge of the structure, biology, biochemistry and physics of the ECM has increased in recent years. We hope that showcasing the ECM to our readers will promote research that improves our understanding of this molecular mesh, and aid scientists as they aim to exploit it in medical applications (such as tissue engineering) and target it in disease.
Research Highlights
Technique: DNA hairpins track traction
doi:10.1038/nrm3905
Nature Reviews Molecular Cell Biology 15, 765 (2014)
Extracellular matrix: Preconditioning the ECM for fibrosis
doi:10.1038/nrm3906
Nature Reviews Molecular Cell Biology 15, 766 (2014)
Journal Club
The needle in the ECM haystack | PDF (583 KB)
p769 | doi:10.1038/nrm3899
Karl E. Kadler describes why the mechanism of collagen fibril assembly in vivo remains elusive.
IN BRIEF
Cell migration: Moving towards ECM with LKB1 | PDF (563 KB)
p767 | doi:10.1038/nrm3911
Nature Reviews Molecular Cell Biology 15, 767 (2014)
Cell adhesion: Basement membranes stick together | PDF (563 KB)
p767 | doi:10.1038/nrm3912
Nature Reviews Molecular Cell Biology 15, 767 (2014)
Foreword
Stretching the boundaries of extracellular matrix research
Richard O. Hynes
doi:10.1038/nrm3908
Nature Reviews Molecular Cell Biology 15, 761 (2014)
Reviews
Extracellular matrix assembly: a multiscale deconstruction
Janna K. Mouw, Guanqing Ou & Valerie M. Weaver
doi:10.1038/nrm3902
Nature Reviews Molecular Cell Biology 15, 771 (2014)
The molecules that are associated with the extracellular matrix (ECM) in different tissues, including collagens, proteoglycans, laminins and fibronectin, and the manner in which they are assembled, determine the structure and the organization of the ECM. The resultant biochemical and biophysical properties of the ECM dictate its tissue-specific functions.
Remodelling the extracellular matrix in development and disease
Caroline Bonnansa, Jonathan Choua & Zena Werb
doi:10.1038/nrm3904
Nature Reviews Molecular Cell Biology 15, 786 (2014)
The extracellular matrix (ECM) regulates many cellular functions, and its remodelling by enzymes such as metalloproteinases has a crucial role during development, as exemplified by intestinal, lung, mammary gland and submandibular gland morphogenesis. ECM structure and composition are important therapeutic targets, as their dysregulation contributes to conditions such as fibrosis and invasive cancer.
Mechanotransduction and extracellular matrix homeostasis
Jay D. Humphrey, Eric R. Dufresne & Martin A. Schwartz
doi:10.1038/nrm3896
Nature Reviews Molecular Cell Biology 15, 802 (2014)
In soft connective tissues at the steady state, cells continually read environmental cues and respond to promote mechanical homeostasis of the extracellular matrix and ensure cellular and tissue health. Progress has been made into our understanding of the molecular, cellular and tissue scale responses to mechanical load that promote mechanical homeostasis.
Physical influences of the extracellular environment on cell migration
Guillaume Charras & Erik Sahai
doi:10.1038/nrm3897
Nature Reviews Molecular Cell Biology 15, 813 (2014)
The physical properties of the extracellular environment — in terms of confinement, rigidity, surface topology and adhesion-ligand density — can have profound effects on the migration strategy and migration velocity of cells in different in vivo contexts.
Perspectives
Appreciating force and shape — the rise of mechanotransduction in cell biology
Thomas Iskratsch, Haguy Wolfenson & Michael P. Sheetz
doi:10.1038/nrm3903
Nature Reviews Molecular Cell Biology 15, 825 (2014)
The form of vertebrates is shaped by the sensing and relaying of mechanical forces that are applied between cells and their microenvironment. Mechanobiology has emerged as a field of research dedicated to studying these forces and their communication through signalling processes, which are collectively known as mechanotransduction.
© 2018 Macmillan Publishers Limited, part of Springer Nature. All Rights Reserved.
