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.

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