Collective durotaxis along a self-generated stiffness gradient in vivo

Nature, Journal Year: 2021, Volume and Issue: 600(7890), P. 690 - 694

Published: Dec. 8, 2021

Language: Английский

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The Extracellular Matrix in Skin Inflammation and Infection

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: July 6, 2021

The extracellular matrix (ECM) is an integral component of all organs and plays a pivotal role in tissue homeostasis repair. While the ECM was long thought to mostly have passive functions by providing physical stability tissues, detailed characterization its structure biochemical properties uncovered unprecedented broad spectrum functions. It now clear that not only comprises essential building block tissues but also actively supports maintains dynamic interplay between compartments as well embedded resident recruited inflammatory cells response pathologic stimuli. On other hand, certain pathogens such bacteria viruses evolved strategies exploit structures for infection mutations proteins can give rise variety genetic conditions. Here, we review composition, function cutaneous homeostasis, skin diseases psoriasis atopic dermatitis infections paradigm understanding wider human health.

Language: Английский

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Targeting Rho GTPase Signaling Networks in Cancer

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: April 3, 2020

As key regulators of cytoskeletal dynamics, Rho GTPases coordinate a wide range cellular processes, including cell polarity, migration and cycle progression. The adoption pro-migratory phenotype enables cancer cells to invade the stroma surrounding primary tumour move towards enter blood or lymphatic vessels. Targeting these early events could reduce progression metastatic disease, leading cause cancer-related deaths. play role in formation dynamic actin-rich membrane protrusions turnover cell-cell cell-extracellular matrix adhesions required for efficient invasion. Here, we discuss roles cancer, their validation as therapeutic targets challenges developing clinically viable GTPase inhibitors. We review other wider signalling network focus on four best characterised effector families: p21-activated kinases (PAKs), Rho-associated protein (ROCKs), atypical kinase Cs (aPKCs) myotonic dystrophy kinase-related Cdc42-binding (MRCKs).

Language: Английский

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The extracellular matrix viscoelasticity as a regulator of cell and tissue dynamics

Current Opinion in Cell Biology, Journal Year: 2021, Volume and Issue: 72, P. 10 - 18

Published: May 13, 2021

Language: Английский

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Endothelial-Mesenchymal Transition in Cardiovascular Disease

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2021, Volume and Issue: 41(9), P. 2357 - 2369

Published: July 1, 2021

Endothelial-to-mesenchymal transition is a dynamic process in which endothelial cells suppress constituent properties and take on mesenchymal cell behaviors. To begin the process, loosen their cell-cell junctions, degrade basement membrane, migrate out into perivascular surroundings. These initial behaviors reflect transient modulation of cellular phenotype, that is, phenotypic modulation, sometimes referred to as partial endothelial-to-mesenchymal transition. Loosening junctions migration are also seen inflammatory angiogenic settings such initiating have overlapping gene expression with responding signals or sprouting form new blood vessels. Reduced increase permeability, facilitates leukocyte trafficking, whereas precedes neovascularization; both barriers quiescence restored stimuli subside. Complete proceeds beyond characteristics become prominent functions diminish. In proadaptive, regenerative produce extracellular matrix contribute tissue integrity maladaptive, pathologic fibrotic, overproducing cause stiffness, eventually impacts function. Here we will review what known about how TGF (transforming growth factor) β influences this continuum from junctional loosening its relevance cardiovascular diseases.

Language: Английский

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Cell–3D matrix interactions: recent advances and opportunities

Trends in Cell Biology, Journal Year: 2022, Volume and Issue: 32(10), P. 883 - 895

Published: April 8, 2022

The diversity of hundreds extracellular matrix (ECM) molecules in different tissues and their interactions are now being documented 'matrisome' databases.Physical properties the 3D ECM, including viscoelasticity microarchitecture, can govern cell adhesion, mechanotransduction, multiple modes migration.New advances ECM biology identifying mechanisms cancer progression fibrosis, as well potential therapeutic targets.Characterizations cell–ECM feedback loops computational modeling providing new insights opportunities for intervention diseases disorders. Tissues consist cells surrounding (ECM). Cell–ECM play crucial roles embryonic development, differentiation, tissue remodeling, fibrosis cancer. Recent research characterizing cell–matrix include detailed descriptions associated molecules, complex intermolecular development disease, identification distinctive migration ECMs, into organ formation. Exploring physical features microenvironments bidirectional regulation signaling organization emphasize dynamic nature these interactions, which that exacerbate disease. Understanding potentially lead to targeted interventions. New on interactionsThe with (see Glossary) during formation adult homeostasis, pathogenesis such This field has expanded explosively after discovery many surface receptors. Our goal this brief review is highlight recent conceptual experimental should provide exciting future cell–3D interactions.Diversity interactionsA starting ~2019 been widespread adoption term – is, comprising it changes disease pathogenesis. holistic concept matrisomes moves beyond classical studies focusing a single protein or family not only structural proteins, collagens, elastin, proteoglycans, fibronectin, but also matrix-associated enzymes inhibitors, matrix-bound growth factors, some cases receptors [1.Karamanos N.K. et al.A guide composition functions matrix.FEBS J. 2021; 288: 6850-6912Crossref PubMed Scopus (65) Google Scholar,2.Izzi V. al.Pan-cancer analysis genomic alterations mutations matrisome.Cancers (Basel). 2020; 12: 2046Crossref (27) Scholar]. Among examples, have used matrisome analyses characterize basement membranes (https://bmbase.manchester.ac.uk/), discover ECM-associated genes more than other [2.Izzi Scholar], identify thrombospondin tenascin links collagen alignment breast [3.Tomko L.A. al.Targeted identifies thrombospondin-2 tenascin-C aligned stroma from invasive carcinoma.Sci. Rep. 2018; 8: 12941Crossref (37) bioengineered models human pancreatic [4.Osuna de la Pena D. al.Bioengineered recapitulate vivo tumour biology.Nat. Commun. 5623Crossref (11) Scholar].Many publications still at descriptive level. There considerable overlaps between components 'adhesome,' comprises adhesions, especially focal adhesions (e.g., see www.adhesome.org). Both 'omics' approaches major applying increasingly sophisticated methods understand involving networks rather just few selected proteins past. Unexpected findings may arise terms groups regulating components. Exemplifying crosstalk, planar membrane two its biochemically unrelated constituents, laminin IV, strongly regulate assembly fibrillar component, variety types [5.Lu al.Basement regulates fibronectin using sliding driven by contractile winch.Dev. Cell. 52: 631-646 e634Abstract Full Text PDF (24) Scholar].We know vary widely depending type biochemical mechanical (Figure 1). Multiple characterized recently range lamellipodial characteristic mesenchymal fibroblast-like rounded amoeboid immune certain [6.Bodor D.L. al.Of shapes motion: basis animal migration.Dev. 550-562Abstract (45) Scholar,7.Yamada K.M. Sixt M. Mechanisms migration.Nat. Rev. Mol. Cell Biol. 2019; 20: 738-752Crossref (262) lobopodial cross-linked linearly elastic spatially confined intracellular pressure, cortical actin flow, ion fluxes, [8.Zhao R. al.Cell sensing decision-making confinement: role TRPM7 tug war hydraulic pressure cross-sectional area.Sci. Adv. 5eaaw7243Crossref (35) Scholar, 9.Patel S. al.Myosin II Arp2/3 cross-talk governs lamellipodia formation.Mol. 32: 579-589Crossref 10.Ullo M.F. Logue J.S. ADF cofilin-1 collaborate promote flow leader bleb-based cells.eLife. 10e67856Crossref (6) 11.Reversat A. al.Cellular locomotion environmental topography.Nature. 582: 582-585Crossref (69) 12.Yolland L. al.Persistent polarized global essential directionality 21: 1370-1381Crossref (22) Scholar].The microarchitecture affect differentiation [13.Doyle A.D. al.Local microenvironment through spatiotemporal dynamics contractility-dependent adhesions.Nat. 2015; 6: 8720Crossref (268) Scholar,14.Seo B.R. al.Collagen mechanically controls myofibroblast differentiation.Proc. Natl. Acad. Sci. U. 117: 11387-11398Crossref (58) For example, networks, fiber thickness pore size, adipose stromal toward process independent overall stiffness previously known stem [14.Seo Scholar,15.Chaudhuri O. al.Effects cellular behaviour.Nature. 584: 535-546Crossref (427) Scholar].Matrix propertiesThe local migratory speed show differences molecular elasticity [15.Chaudhuri Examining whether an soft stiff numerous previous [16.Hayward M.K. al.Tissue mechanics fate, cancer.Dev. 56: 1833-1847Abstract (20) Scholar,17.Xue B. al.Engineering hydrogels homogeneous controlling lineage specification.Proc. 118e2110961118Crossref (13) Scholar] ideally be complemented behavior environments differing viscoelasticity. reason biological matrices often viscoelastic, they display combination viscosity thick fluid attempts return material original form deforming force released. results plastic deformation slipping, creep 'stress relaxation' response deformed, without returning form. Viscoelasticity modulated extent crosslinking property effects behavior, although underlying yet clear. altered rheology filopodial versus protrusions leading edge cell, rates spreading migration, processes morphogenesis, epithelial-mesenchymal transition, invasion, [18.Adebowale K. al.Enhanced substrate stress relaxation promotes filopodia-mediated Mater. 1290-1299Crossref (36) 19.Gong Z. al.Matching timescales maximizes viscoelastic substrates.Proc. 115: E2686-E2695Crossref (129) 20.Wisdom al.Matrix plasticity confining microenvironments.Nat. 9: 4144Crossref (162) 21.Yang mechanosensing synthetic controlled biophysical dynamics.Nat. 3514Crossref 22.Indana al.Viscoelasticity adhesion biomaterials control pluripotent morphogenesis culture.Adv. 33e2101966Crossref (17) 23.Chang A.C. al.Precise tuning characterization interfaces study early transition behaviors.Langmuir. 2022; (Published online February 10, 2022)https://doi.org/10.1021/acs.langmuir.1c03048Crossref (3) 24.Hui E. al.The combined influence adhesive cues fibroblast organization.Cell. Bioeng. 14: 427-440Crossref (9) fact chemical substantially alter mode, speed, means one cannot simply 'work 3D' due factors An ongoing challenge will generate accurately mimic specific use ex tissues. Development physiological simple gels current valuable accurate platforms testing translational approaches.MechanotransductionDifferent elicit distinct responses cells. 2D revealed test repetitively probing [25.Plotnikov S.V. al.Force fluctuations within mediate ECM-rigidity directed migration.Cell. 2012; 151: 1513-1527Abstract (559) analogous hikers footing when crossing unstable terrain. Cells sense respond ECM-transmitted forces tension involves integrin-based where actomyosin-mediated transmitted substrata [26.Zuidema al.Crosstalk complexes mechanotransduction.Bioessays. 42e2000119Crossref (31) Scholar,27.Doyle al.Cell-extracellular dynamics.Phys. 19https://doi.org/10.1088/1478-3975/ac4390Crossref (8) In environments, mechanotransduction level resembles under conditions stiffer substrates stabilize while softer, flexible shorter lifetimes faster Scholar].Mechanotransduction becomes particularly concerning cycle. evidence fibroblasts migrating reveals prior translocation, initially deform (prestrain) fibrils, increasing self-generated contracting transmitting essentially first 'pulling up slack rope' (i.e., fibrils [28.Doyle al.3D anterior contraction generates prestrain.Dev. 826-841.e4Abstract Scholar]). Interestingly, epithelial relatively equal-and-opposite strain transmission posterior directions 2A ) [29.Hall M.S. al.Fibrous nonlinear enables positive ECMs.Proc. 2016; 113: 14043-14048Crossref (174) (nonepithelial) cancers constant prestrains twofold greater front rear suggesting disconnect propagation 2A) prestrain likely genetically primed contractility-centric mode higher expression myosin II) enhanced microenvironment. sequence events distinctive, actomyosin contractions preceding leading-edge protrusive activity, helps establish unique cycle 2B–C) Discrepancies cycles importance conditions.Figure 2Mechanotransduction migration.Show full caption(A) Schematic showing directionally gels. Mesenchymal (left) high extensive integrin ligation large strains larger rear. Similar attributes seen fibrosarcoma cells, majority (right) smaller, transient rear, lower graph summarizing latter concept, requires further testing). (B C) schematic shows matrix. Yellow arrows depict directional applied matrix, magenta indicate relative summed given region. During cycle, (C) retrograde pull stabilizes (gray ovals) edge. A contralateral anterograde (increased direction migration) leads pinching followed increase protrusion (broken white line). Abbreviation: matrix.View Large Image Figure ViewerDownload Hi-res image Download (PPT)In addition, (elastic etc.) alters mechanotransduction. suggest ECMs Viscoelastic effective eliciting compared Future evaluate interacting properties, vitro microenvironments.The nucleus migrationSome 'nuclear piston' pulled anteriorly contractility pressurize drive 'lobopodial' forward [30.Petrie R.J. al.Activating nuclear piston mechanism tumor cells.J. 2017; 216: 93-100Crossref (63) (plastic), mechanosensitive channels generated elevated hydrostatic triggering channel activation; resulting influx sodium calcium ions enhances osmotic provides additional extending promoting efficient [31.Lee H.P. activates paths microenvironments.Sci. 7eabd4058Google Scholar].Another intriguing finding stiff, bulky ruler help choice wider, readily traversed passageway [32.Renkawitz al.Nuclear positioning facilitates along path least resistance.Nature. 568: 546-550Crossref (125) Scholar,33.Lomakin A.J. acts tailoring spatial constraints.Science. 370eaba2894Crossref (110) Besides serving ruler, conjunction cytoskeleton function, gauge activate epigenetic pathways 3) Scholar,34.Venturini measures shape proprioception behavior.Science. 370eaba2644Crossref (102) 35.Maurer Lammerding driving force: disease.Annu. Biomed. Eng. 443-468Crossref (80) 36.Alisafaei F. al.Regulation architecture, mechanics, nucleocytoplasmic shuttling geometric constraints.Proc. 116: 13200-13209Crossref (82) Scholar].Figure 3Multiple mechanosensing, mechanotransduction.Show captionThe nucleus, largest organelle, function entry narrow spaces channels. contraction, thereby termed lobopodia. serve sensor responding confinement. Finally, signal transducer initiating gene expression.View (PPT)Cancer dynamicsCancer invasion continues another very active investigation various ECM. Before malignant invade interstitial tissues, must usually breach barrier surrounds 4). Although proteases degrade protease-independent breaching occur. Physical extension penetrate expand holes ATP production Caenorhabditis elegans [37.Kelley L.C. al.Adaptive F-actin polymerization localized absence MMPs.Dev. 48: 313-328.e8Abstract Human nonproteolytic repetitive microspikes widen filopodia enlarging perforations; protruding subsequently probe [38.Chang Chaudhuri Beyond proteases: invasion.J. 218: 2456-2469Crossref 39.Eschenbruch al.From fibers: remodeling acini drives II-mediated invasion.Cells. 10: 1979Crossref 40.Gong al.Recursive dissipation chemo-mechanical oscillatory invadopodia.Cell 35109047Abstract Cellular metabolic activation important successful crosstalk Scholar,41.Zanotelli M.R. al.Mechanoresponsive metabolism metastasis.Cell Metab. 33: 1307-1321Abstract 42.Romani P. metabolism.Nat. 22: 22-38Crossref (94) 43.Torrino al.Mechano-induced microtubule glutamylation 1342-1357.e10Abstract (18) 4Different membrane.Show captionCancer transiently barriers mechanisms. proteases, metalloproteinases (MMPs), locally, MMPs tips invadopodia. Even if inhibited, tiny perforations requiring energy (orange shading) (yellow arrows) push laterally ridge around expanding hole (red mounds). both processes, proteolysis perforations.View (PPT)Although generation thought involve contractility, relationship levels nonmuscle invasiveness complex. Some isoforms actomyosin-associated predicted facilitate others decreased consistent suppressor Scholar,44.Parajon mechanobiome: goldmine therapeutics.Am. Physiol. 320: C306-C323Crossref Scholar,45.Picariello H.S. IIA suppresses glioblastoma sensitive manner.Proc. 15550-15559Crossref (25) bifunctional complexity myosin-X enhancing suppressing modulating [46.Peuhu al.Myosin-X-dependent limits invasion.bioRxiv. October 22, 2021)https://doi.org/10.1101/2021.10.22.464987Google Scholar].Although obvious source disrupting structure breaching, contributor lateral branches density [47.Papalazarou Maches

Language: Английский

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The amoeboid state as part of the epithelial-to-mesenchymal transition programme

Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 32(3), P. 228 - 242

Published: Nov. 23, 2021

Cell migration is essential for many biological processes, while abnormal cell characteristic of cancer cells. Epithelial cells become motile by undergoing epithelial-to-mesenchymal transition (EMT), and mesenchymal increase speed adopting amoeboid features. This review highlights how behaviour not merely a mode but rather cellular state - within the EMT spectra which survive, invade colonise challenging microenvironments. Molecular biomarkers physicochemical triggers associated with are discussed, including an tumour microenvironment. We reflect on characteristics support metastasis their liabilities could turn into therapeutic opportunities.

Language: Английский

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Mechanics of 3D Cell–Hydrogel Interactions: Experiments, Models, and Mechanisms

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(18), P. 11085 - 11148

Published: Sept. 2, 2021

Hydrogels are highly water-swollen molecular networks that ideal platforms to create tissue mimetics owing their vast and tunable properties. As such, hydrogels promising cell-delivery vehicles for applications in engineering have also emerged as an important base ex vivo models study healthy pathophysiological events a carefully controlled three-dimensional environment. Cells readily encapsulated resulting plethora of biochemical mechanical communication mechanisms, which recapitulates the natural cell extracellular matrix interaction tissues. These interactions complex, with multiple invariably coupled spanning length time scales. To identify underlying mechanisms involved, integrated experimental computational approach is ideally needed. This review discusses state our knowledge on cell–hydrogel interactions, focus mechanics transport, this context, highlights recent advancements experiments, mathematical modeling. The begins background thermodynamics physics fundamentals govern hydrogel transport. focuses two main classes hydrogels, described semiflexible polymer represent physically cross-linked fibrous flexible representing chemically synthetic hydrogels. In review, we highlight five involve key cellular functions related communication, mechanosensing, migration, growth, deposition elaboration. For each these functions, experiments most up date modeling strategies discussed then followed by summary how tune properties achieve desired functional outcome. We conclude linking make case need integrate advance fundamental understanding cell–matrix will ultimately help new therapeutic approaches enable successful engineering.

Language: Английский

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The spatio-temporal control of effector T cell migration

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(9), P. 582 - 596

Published: Feb. 24, 2021

Language: Английский

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Extracellular vesicles: Critical players during cell migration

Developmental Cell, Journal Year: 2021, Volume and Issue: 56(13), P. 1861 - 1874

Published: April 2, 2021

Language: Английский

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