Adhesion dynamics: Mechanisms and measurements (original) (raw)
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Advances in imaging cell-matrix adhesions
Journal of Cell Science, 2010
Adhesion is fundamental to the survival and function of many different cell types, and regulates basic events such as mitosis, cell survival and migration, in both embryonic and adult organisms. Cell-matrix adhesion also regulates the dynamic interplay between cells and surrounding tissues during processes such as immune cell recruitment, wound healing and cancer cell metastasis. The study of cell adhesion has gained momentum in recent years, in large part because of the emergence of imaging techniques that have facilitated detailed analysis of the molecular composition and dynamics of the structures involved. In this Commentary, we discuss the recent application of different imaging techniques to study cell-matrix adhesions, emphasising common strategies used for the analysis of adhesion dynamics both in cells in culture and in whole organisms.
The Molecular Architecture of Cell Adhesion: Dynamic Remodeling Revealed by Videonanoscopy
Frontiers in Cell and Developmental Biology, 2016
The plasma membrane delimits the cell, which is the basic unit of living organisms, and is also a privileged site for cell communication with the environment. Cell adhesion can occur through cell-cell and cell-matrix contacts. Adhesion proteins such as integrins and cadherins also constitute receptors for inside-out and outside-in signaling within proteolipidic platforms. Adhesion molecule targeting and stabilization relies on specific features such as preferential segregation by the sub-membrane cytoskeleton meshwork and within membrane proteolipidic microdomains. This review presents an overview of the recent insights brought by the latest developments in microscopy, to unravel the molecular remodeling occurring at cell contacts. The dynamic aspect of cell adhesion was recently highlighted by super-resolution videomicroscopy, also named videonanoscopy. By circumventing the diffraction limit of light, nanoscopy has allowed the monitoring of molecular localization and behavior at the single-molecule level, on fixed and living cells. Accessing molecular-resolution details such as quantitatively monitoring components entering and leaving cell contacts by lateral diffusion and reversible association has revealed an unexpected plasticity. Adhesion structures can be highly specialized, such as focal adhesion in motile cells, as well as immune and neuronal synapses. Spatiotemporal reorganization of adhesion molecules, receptors, and adaptors directly relates to structure/function modulation. Assembly of these supramolecular complexes is continuously balanced by dynamic events, remodeling adhesions on various timescales, notably by molecular conformation switches, lateral diffusion within the membrane and endo/exocytosis. Pathological alterations in cell adhesion are involved in cancer evolution, through cancer stem cell interaction with stromal niches, growth, extravasation, and metastasis.
The structure of cell–matrix adhesions: the new frontier
Current Opinion in Cell Biology, 2012
Adhesions between the cell and the extracellular matrix (ECM) are mechanosensitive multiprotein assemblies that transmit force across the cell membrane and regulate biochemical signals in response to the chemical and mechanical environment. These combined functions in force transduction, signaling and mechanosensing contribute to cellular phenotypes that span development, homeostasis and disease. These adhesions form, mature and disassemble in response to actin organization and physical forces that originate from endogenous myosin activity or external forces by the extracellular matrix. Despite advances in our understanding of the protein composition, interactions and regulation, our understanding of matrix adhesion structure and organization, how forces affect this organization, and how these changes dictate specific signaling events is limited. Insights across multiple structural levels are acutely needed to elucidate adhesion structure and ultimately the molecular basis of signaling and mechanotransduction. Here we describe the challenges and recent advances and prospects for unraveling the structure of cellmatrix adhesions and their response to force. Cell-matrix adhesions are a collection of discrete entities Cell matrix adhesions were first identified over 40 years ago [1]. Their complex structure and diverse function, however, took a while to unfold. They were first observed as discrete, focal regions in close apposition to the substratum using interference reflection microscopy. A decade later, correlative light and conventional electron microscopy showed actin filament bundles terminating or emanating from these adhesions revealing a connection between the ECM and the actin cytoskeleton [2]. Antibodies raised against molecules purified from chicken gizzard smooth muscle, e.g., α-actinin, vinculin, and talin, localized specifically to these adhesion sites, thus ushering the molecular era of adhesion research [3-7]. Subsequently, a plethora of other adhesion components have been identified by their localization to adhesions [8]. They include specific ECM components, like fibronectin, the transmembrane integrin receptors that link cytoplasmic actin to the matrix, and a large number of molecules involved in signal transduction. This structural complexity is reflected in the diverse functions mediated by adhesions, e.g., cytoskeletal organization and contraction, regulation of proliferation, cell survival, gene expression, protrusion (migration), and adhesion [9,10].
Imaging of cell adhesion events in 3D matrix environments
European Journal of Cell Biology, 2012
Cell adhesion plays an essential role in development and homeostasis, but is also a key regulator of many diseases such as cancer and immune dysfunction. Numerous studies over the past three decades have revealed a wealth of information detailing signalling molecules required for cell adhesion to twodimensional surfaces. However, in vivo many cells are completely surrounded by matrix and this will very likely influence the size, composition and dynamics of adhesive structures. The study of adhesion in cells within three-dimensional environments is still in its infancy, thus the role and regulation of adhesions in these complex environments remains unclear. The recent development of new experimental models coupled with significant advances in cell imaging approaches have provided platforms for researchers to begin to dissect adhesion signalling in cells in 3D matrices. Here we summarise the recent insights in cell adhesion formation and regulation in 3D model systems and the imaging approaches used to analyse these events. (M. Parsons). a tight and controlled regulation of these processes is needed in order to drive effective forward movement . Adherent cells plated on an ECM-coated rigid surface initially form small, dot-like adhesive contacts called nascent adhesions formed by small clusters (<0.25 mm) of integrins, integrin activators, such as talin, and adaptor proteins, like paxillin . Integrins are a family of 24 ␣ heterodimeric receptors in mammals with a different affinity for ECM components. They can be activated by intracellular factors, such as talin and kindlins, but they are also primary docking sites for matrix-dependent outside-in signalling that acts to recruit a myriad of proteins to control adhesion maturation, disassembly and cytoskeletal dynamics . As the cell moves forward, nascent adhesions can undergo a maturation process to form focal complexes that are larger in size (∼0.5 m), have longer lifetimes and depend upon non-muscle myosin II (NMII) for assembly . Increased tension induces the recruitment of mechano-sensory and signalling proteins such as vinculin and ␣-actinin, and the focal complexes can enlarge in size and show a more stable phenotype to become a focal adhesion (FA) . FAs display a more elongated morphology and wider size range (between 1 and 5 m) and they progressively change their integrin composition from 3 in focal complexes to 1 integrins, which tend to localise more in the cell body. Proteins such as focal adhesion kinase (FAK), VASP and Src among others are recruited to mature adhesions and these molecules play a role in co-ordinating disassembly. In this process, as before, localised cell tension within substrate plays an essential role in maturation process ( and C) (Scales and Parsons, 2011; Vicente-Manzanares and Horwitz,
This study establishes that the physical state of the extracellular matrix can regulate integrinmediated cytoskeletal assembly and tyrosine phosphorylation to generate two distinct types of cell-matrix adhesions. In primary fibroblasts, ␣ 5  1 integrin associates mainly with fibronectin fibrils and forms adhesions structurally distinct from focal contacts, independent of actomyosinmediated cell contractility. These "fibrillar adhesions" are enriched in tensin, but contain low levels of the typical focal contact components paxillin, vinculin, and tyrosine-phosphorylated proteins. However, when the fibronectin is covalently linked to the substrate, ␣ 5  1 integrin forms highly tyrosine-phosphorylated, "classical" focal contacts containing high levels of paxillin and vinculin. These experiments indicate that the physical state of the matrix, not just its molecular composition, is a critical factor in defining cytoskeletal organization and phosphorylation at adhesion sites. We propose that molecular organization of adhesion sites is controlled by at least two mechanisms: 1) specific integrins associate with their ligands in transmembrane complexes with appropriate cytoplasmic anchor proteins (e.g., fibronectin-␣ 5  1 integrin-tensin complexes), and 2) physical properties (e.g., rigidity) of the extracellular matrix regulate local tension at adhesion sites and activate local tyrosine phosphorylation, recruiting a variety of plaque molecules to these sites. These mechanisms generate structurally and functionally distinct types of matrix adhesions in fibroblasts. † Present address:
Recent Advances and Prospects in the Research of Nascent Adhesions
Frontiers in Physiology, 2020
Nascent adhesions are submicron transient structures promoting the early adhesion of cells to the extracellular matrix. Nascent adhesions typically consist of several tens of integrins, and serve as platforms for the recruitment and activation of proteins to build mature focal adhesions. They are also associated with early stage signaling and the mechanoresponse. Despite their crucial role in sampling the local extracellular matrix, very little is known about the mechanism of their formation. Consequently, there is a strong scientific activity focused on elucidating the physical and biochemical foundation of their development and function. Precisely the results of this effort will be summarized in this article.