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| Open AccessAge-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture
Neural circuit architecture must be maintained during an animal’s lifetime. Here, the authors show that a protective mechanism combining proteostasis and biomechanics supports the integrity of glial cells to environmental stressors.
- Francesca Coraggio
- , Mahak Bhushan
- & Georgia Rapti
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Article
| Open AccessGenome-wide screens identify SEL1L as an intracellular rheostat controlling collagen turnover
Mechanisms regulating collagen clearance may be useful for treating fibrosis. Here, the authors conducted functional genome-wide screens and found that collagen biosynthesis directly regulates collagen clearance via a noncanonical function of SEL1L.
- Michael J. Podolsky
- , Benjamin Kheyfets
- & Kamran Atabai
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Article
| Open AccessIntercellular transfer of cancer cell invasiveness via endosome-mediated protease shedding
The matrix metalloprotease MT1-MMP drives cancer metastasis. Here, the authors demonstrate how invasive cancer cells instigate non-invasive neighbouring cells to become degradative and invasive by transferring catalytically active MT1-MMP fragments.
- Eva Maria Wenzel
- , Nina Marie Pedersen
- & Camilla Raiborg
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| Open AccessLongevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans
Mechanotransduction can be defined as translating physical forces into gene expression, which subsequently drives cell fate. Here, Teuscher et al. showed that mechanotransduction across multiple tissues and extracellular matrices is essential for promoting longevity in vivo.
- Alina C. Teuscher
- , Cyril Statzer
- & Collin Y. Ewald
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Article
| Open AccessHuman apical-out nasal organoids reveal an essential role of matrix metalloproteinases in airway epithelial differentiation
Airway organoids made in Matrigel are in basal-out orientation. Here, authors present apical-out nasal organoids using a biochemically defined hydrogel system, revealing that matrix metalloproteinases are required for normal epithelial development.
- Liyue Li
- , Linyi Jiao
- & Chunwei Li
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Article
| Open AccessLung extracellular matrix modulates KRT5+ basal cell activity in pulmonary fibrosis
Idiopathic pulmonary fibrosis has been associated with aberrant expansion of KRT5-expressing basal cells. Here the authors show how changes in the ECM glycoprotein SPARC restrict the movement of KRT5+ cells, affecting their retention within fibrotic tissue.
- Richard J. Hewitt
- , Franz Puttur
- & Clare M. Lloyd
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Article
| Open AccessAlk1 acts in non-endothelial VE-cadherin+ perineurial cells to maintain nerve branching during hair homeostasis
Vascular endothelial (VE)-cadherin is a well-recognized endothelial cell marker. Here, the authors unveil unexpected heterogeneity in the skin VE-cadherin lineage, identifying a dynamic, non-endothelial VE-cadherin+ perineurial cell population.
- Gopal Chovatiya
- , Kefei Nina Li
- & Tudorita Tumbar
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| Open AccessGrowth anisotropy of the extracellular matrix shapes a developing organ
Tissue morphogenesis is a complex process that involves tissue growth, mechanics, and shape changes. This work demonstrates that differences in growth rate and direction between a tissue layer and its associated extracellular matrix drive 3D shape changes during organ growth.
- Stefan Harmansa
- , Alexander Erlich
- & Thomas Lecuit
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Article
| Open AccessDesign of synthetic collagens that assemble into supramolecular banded fibers as a functional biomaterial testbed
Molecular level control is required to capture the folding and supramolecular assembly of collagen in mimetic materials. Here, the authors report on the creation of a synthetic collagen which assembles into banded fibers, recaptures structural properties of natural collagen and which can act as a testbed for design and experimentation
- Jinyuan Hu
- , Junhui Li
- & Fei Xu
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Article
| Open AccessThe Hippo pathway links adipocyte plasticity to adipose tissue fibrosis
Adipose tissue fibrosis is connected to obesity-related metabolic dysfunction. Qiu and colleagues discover that the Hippo pathway acts as a molecular switch in the initiation and development of adipose tissue fibrosis upon TGFβ stimulation.
- Hongyu Shen
- , Xun Huang
- & Yifu Qiu
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| Open AccessAirway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis
The functional role of airway basal cells has not been comprehensively studied in idiopathic pulmonary fibrosis (IPF). Here, the authors show that airway basal cells of IPF patients display a distinct phenotype, are profibrotic if transplanted to mice and that fibrosis can be ameliorated by Src iinhibitors.
- Benedikt Jaeger
- , Jonas Christian Schupp
- & Antje Prasse
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| Open AccessSpatially resolved proteomic map shows that extracellular matrix regulates epidermal growth
Ling Leng et al. construct a hierarchical skin proteome map and identify an extracellular matrix glycoprotein TGFBI, which is located in basement membrane and could enhance the growth and function of epidermal stem cells and promote wound healing.
- Jun Li
- , Jie Ma
- & Ling Leng
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Article
| Open AccessCell surface glycan engineering reveals that matriglycan alone can recapitulate dystroglycan binding and function
Matriglycan, a repeating disaccharide on α-dystroglycan, is the receptor for Lassa virus and specific extracellular matrix proteins. Here, the authors demonstrate that matriglycan, in a length-dependent tunable manner, is both necessary and sufficient for protein binding and viral infection.
- M. Osman Sheikh
- , Chantelle J. Capicciotti
- & Geert-Jan Boons
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| Open AccessTransgenic Anopheles mosquitoes expressing human PAI-1 impair malaria transmission
Plasmodium gametes and sporozoites activate surface-bound plasminogen to plasmin that degrades extracellular matrix barriers, therewith facilitating parasite motility in mosquitoes and mammalian hosts. To control malaria transmission, Pascini et al. generate Anopheles stephensi transgenic mosquitoes constitutively secreting human plasminogen activator inhibitor 1 in midgut and/or saliva which leads to inhibition of plasminogen activation and a reduction in oocyst intensity, infection prevalence, and transmission.
- Tales V. Pascini
- , Yeong Je Jeong
- & Joel Vega-Rodríguez
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| Open AccessTopography-induced large-scale antiparallel collective migration in vascular endothelium
The physical environment dictates the emergence of specific patterns of collective cell migration. Here, authors show that unconfined endothelial monolayers on microgroove substrates exhibit an original pattern of antiparallel cell streams.
- Claire Leclech
- , David Gonzalez-Rodriguez
- & Abdul I. Barakat
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Article
| Open AccessPPARα−ACOT12 axis is responsible for maintaining cartilage homeostasis through modulating de novo lipogenesis
Increasing evidence suggested that dysregulation in lipid metabolism is linked to OA pathogenesis, but the underlying regulatory mechanism is not well understood. Here, the authors show that PPARα-ACOT12 signalling regulates cartilage homeostasis by regulating de novo lipogenesis in mice.
- Sujeong Park
- , In-Jeoung Baek
- & Eun-Jung Jin
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Article
| Open AccessType-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta
Collagen is the most abundant protein in the human body. Here, the authors show that different classes of fibroblasts produce collagen of unique functions with different impacts on embryo development and bone formation.
- Yang Chen
- , Sujuan Yang
- & Raghu Kalluri
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Article
| Open AccessAgrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing
Replenishing key extracellular matrix (ECM) proteins facilitate wound healing through unclear mechanisms. Here the authors report that injury-triggered Agrin, an ECM proteoglycan, tunes a mechanocompetent niche by engaging MMP-12, thereby enforcing efficient skin wound healing.
- Sayan Chakraborty
- , Divyaleka Sampath
- & Wanjin Hong
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Article
| Open AccessExtracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity
Basal progenitors are enriched in gyrencephalic species like humans contributing to neuronal expansion. Here the authors show that LGALS3BP de novo variants are related to reduced cortical complexity and area in humans and that LGALS3BP regulates neural progenitor position in organoids, human fetal tissue and mice.
- Christina Kyrousi
- , Adam C. O’Neill
- & Silvia Cappello
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| Open AccessMapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions
The basement membrane is located at tissue interfaces, but how it mediates distinct inter-tissue interactions is unclear. Here, the authors systematically define the spatial heterogeneity of skin basement membrane composition and show its functional importance in inter-tissue interactions.
- Ko Tsutsui
- , Hiroki Machida
- & Hironobu Fujiwara
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| Open AccessProteome-wide and matrisome-specific alterations during human pancreas development and maturation
The pancreatic extracellular matrix (ECM) is known to differ between species, age groups and physiological states, but its compositional changes throughout human life are not well understood. Here, the authors study how the proteome of pancreatic ECM changes during human development and maturation.
- Zihui Li
- , Daniel M. Tremmel
- & Lingjun Li
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| Open AccessExtracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture
Organoid cultures have been developed from multiple tissues, opening new possibilities for regenerative medicine. Here the authors demonstrate the derivation of GMP-compliant hydrogels from decellularized porcine small intestine which support formation and growth of human gastric, liver, pancreatic and small intestinal organoids.
- Giovanni Giuseppe Giobbe
- , Claire Crowley
- & Paolo De Coppi
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| Open AccessEnergetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making
Migrating cells tune their energy utilization in response to their microenvironment, but how cellular energetics direct navigation remains unclear. Here, the authors report that energetic costs for motility, regulated by cell mechanics and confinement, predict the probability of migration choice.
- Matthew R. Zanotelli
- , Aniqua Rahman-Zaman
- & Cynthia A. Reinhart-King
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Article
| Open AccessA small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development
Loss of cartilage tissue is a hallmark of osteoarthritis. Here the authors show that BNTA, a small molecule identified in a chemical screen, promotes ECM generation in human osteoarthritic chondrocytes and cartilage explants, and suppresses pathology in a rat model of osteoarthritis.
- Yuanyuan Shi
- , Xiaoqing Hu
- & Yingfang Ao
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Article
| Open AccessActomyosin contractility-dependent matrix stretch and recoil induces rapid cell migration
How cells migrate in fibrous tissues is still poorly understood. Here, with synthetic 3D fibre matrices of controlled alignment and stiffness, the authors report that cells in stiff matrices move slowly and continuously, but in softer, deformable matrices cells can rapidly slingshot forward via stretch and recoil of matrix fibres.
- William Y. Wang
- , Christopher D. Davidson
- & Brendon M. Baker
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Article
| Open AccessKindlin-2 links mechano-environment to proline synthesis and tumor growth
The mechano-properties of the Extracellular Matrix (ECM) are important for tumorigenesis. Here, the authors show that the stiffening of the ECM promotes translocation of the focal adhesion protein—Kindlin-2—to the mitochondria, where it interacts with the proline synthesis enzyme PYCR1, stimulating proline synthesis and cell proliferation.
- Ling Guo
- , Chunhong Cui
- & Chuanyue Wu
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Article
| Open AccessMacrophage-derived netrin-1 promotes abdominal aortic aneurysm formation by activating MMP3 in vascular smooth muscle cells
Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix degradation. Here Hadi et al. identify a netrin-1/neogenin-based crosstalk between macrophages and vascular smooth muscle cells (VSMCs), leading to the secretion of the matrix metalloproteinase MMP-3 by VSMCs and subsequent matrix degradation in AAA lesions.
- Tarik Hadi
- , Ludovic Boytard
- & Bhama Ramkhelawon
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Article
| Open AccessMyh10 deficiency leads to defective extracellular matrix remodeling and pulmonary disease
Abnormal alveolar development and homeostasis are common features of pulmonary disease. Here the authors show that Myh10 expression is reduced in emphysema patients, and that Myh10 loss of function impairs alveolar formation and lung morphogenesis via upregulation of matrix metalloproteinase activity and altered matrix remodeling.
- Hyun-Taek Kim
- , Wenguang Yin
- & Didier Y. R. Stainier
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Article
| Open AccessLaminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing
Laminins are important regulators of epidermal wound healing. Here, the authors show that laminins bind to multiple growth factors via their heparin-binding domains, and that incorporation of these domains into fibrin matrices increases growth factor retention, promoting wound healing in type 2 diabetic mouse models.
- Jun Ishihara
- , Ako Ishihara
- & Jeffrey A. Hubbell
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Article
| Open AccessMatrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program
Mechanical cues are known to influence endothelial cell behavior. Here Frye et al. show that lymphatic endothelial cell progenitors experience varying degrees of matrix stiffness during development, and that matrix stiffness regulates GATA2 expression to drive lymphatic vessel formation.
- Maike Frye
- , Andrea Taddei
- & Taija Mäkinen
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Article
| Open AccessEGFL7 reduces CNS inflammation in mouse
Endothelial cells release extracellular matrix components that regulate inflammation. Here the authors demonstrate that the extracellular matrix component epidermal growth factor-like protein 7 regulates inflammation in experimental autoimmune encephalomyelitis in the mouse.
- Catherine Larochelle
- , Timo Uphaus
- & Frauke Zipp
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| Open AccessControl of cell morphology and differentiation by substrates with independently tunable elasticity and viscous dissipation
Purely elastic biomimetic soft materials are used to characterize the mechanical response of cells, but do not resemble real tissues. Here the authors develop a viscoelastic solid hydrogel, based on polyacrylamide, that can be tuned to closely resemble soft tissue, and show the influence of viscous dissipation on cellular mechanical sensing.
- Elisabeth E. Charrier
- , Katarzyna Pogoda
- & Paul A. Janmey
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Article
| Open AccessQuantitative structural mechanobiology of platelet-driven blood clot contraction
Blood clot contraction is a cellular (patho)physiological process essential for wound healing, hemostasis, and thrombosis. Here, the authors describe the physical structural mechanism by which platelet filopodia pull “hand-over-hand” on fibrin fibers to compact them into bundled agglomerates.
- Oleg V. Kim
- , Rustem I. Litvinov
- & John W. Weisel
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| Open AccessMatrix degradability controls multicellularity of 3D cell migration
The fabrication of vascularized 3D tissues requires an understanding of how material properties govern endothelial cell invasion into the surrounding matrix. Here the authors integrate a non-swelling synthetic hydrogel with a microfluidic device to study chemokine gradient-driven angiogenic sprouting and find that matrix degradability modulates the collectivity of cell migration.
- Britta Trappmann
- , Brendon M. Baker
- & Christopher S. Chen
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Article
| Open AccessPhysical limits to biomechanical sensing in disordered fibre networks
Cells in the connective tissue are surrounded by a heterogeneous network of biopolymers. Here, the authors investigate how such heterogeneity affects cellular mechanosensing by simulating the deformation response of experimental and modelled biopolymer networks to locally applied forces.
- Farzan Beroz
- , Louise M. Jawerth
- & Ned S. Wingreen
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| Open AccessCMG2/ANTXR2 regulates extracellular collagen VI which accumulates in hyaline fibromatosis syndrome
Hyaline fibromatosis syndrome (HFS) is a hereditary disease characterized by nodular cutaneous lesions and joint pain. Here Bürgiet al. show that CMG2/ANTXR2 regulates collagen VI abundance, with loss-of-function mutations promoting collagen VI accumulation in HFS nodules and myometrial collagen deposition and sterility in mice, which can be rescued by depleting collagen VI.
- Jérôme Bürgi
- , Béatrice Kunz
- & F. Gisou van der Goot
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| Open AccessShifting the optimal stiffness for cell migration
Cell migration is sensitive to environmental stiffness, but how cells sense optimal stiffness is not known. Here the authors develop a model that predicts that the optimum can be shifted by altering the number of active molecular motors and clutches, and verify their model in two cell types.
- Benjamin L. Bangasser
- , Ghaidan A. Shamsan
- & David J. Odde
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Article
| Open AccessConcerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors
Establishment of the outer blood-retina barrier is a hallmark of retinal development but the contribution of choroid endothelial cells (ECs) is not known. Here the authors show in the developing mouse retina that ECs remodel the basement membrane and lead to enhanced barrier function of retinal epithelial cells.
- Ignacio Benedicto
- , Guillermo L. Lehmann
- & Enrique Rodriguez-Boulan
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Article
| Open AccessαV-class integrins exert dual roles on α5β1 integrins to strengthen adhesion to fibronectin
Interaction of fibronectin with αv-class and α5β1 integrins results in formation of cell adhesion complexes, but the initial events (<120 s) remain unclear. Here, the authors show that αv-class integrins bind fibronectin faster than α5β1 integrins and subsequently signal to α5ß1 integrins to strengthen the adhesion.
- Mitasha Bharadwaj
- , Nico Strohmeyer
- & Daniel J. Müller
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Article
| Open AccessFibronectin-guided migration of carcinoma collectives
Tumour microenvironment influences the migration of cancer cells. Here the authors analyse the proteomic constitution of the extracellular matrix and identify a role for fibronectin in regulating the collective migration of squamous cell carcinoma cells.
- Sandeep Gopal
- , Laurence Veracini
- & Ellen Van Obberghen-Schilling
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Article
| Open AccessStructural decoding of netrin-4 reveals a regulatory function towards mature basement membranes
Netrins are secreted guidance factors that promote axon outgrowth and orientation during nervous system development. Here the authors present structural and biological evidence that netrin-4 is not a guidance cue per se, but rather functions to modulate laminin-laminin interactions.
- Raphael Reuten
- , Trushar R. Patel
- & Manuel Koch
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Article
| Open AccessMechanosensing by the α6-integrin confers an invasive fibroblast phenotype and mediates lung fibrosis
Matrix stiffening is a feature of pulmonary fibrosis, and is amplified by lung myofibroblasts. Here the authors find that a6 integrin expression is upregulated on lung myofibroblasts in response to matrix stiffness, and this integrin is required for myofibroblast invasion, and fibrosis in an experimental disease model.
- Huaping Chen
- , Jing Qu
- & Yong Zhou
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Article
| Open AccessRhoA determines lineage fate of mesenchymal stem cells by modulating CTGF–VEGF complex in extracellular matrix
It is unclear what regulates the fate of mesenchymal stem cells (MSCs) in arterial repair following injury. Here, the authors show that MSC differentiation following injury is triggered by RhoA which in turn stimulates the release of connective tissue growth factor and vascular endothelial growth factor.
- Changjun Li
- , Gehua Zhen
- & Mei Wan
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Article
| Open AccessMicrotubule-dependent balanced cell contraction and luminal-matrix modification accelerate epithelial tube fusion
During tracheal tube fusion in Drosophila, a pair of tip cells form an adherens junction and then fuse their plasma membranes. Here the authors show that a balanced pulling force mediated by myosin and microtubules, as well as localized deposition of matrix, promotes plasma membrane fusion.
- Kagayaki Kato
- , Bo Dong
- & Shigeo Hayashi
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Article
| Open AccessCellular forces and matrix assembly coordinate fibrous tissue repair
Planar in vitromodels for wound closure stress the role of lamellipodial protrusions and purse-string contraction. Here the authors develop a 3D biomimetic model for tissue repair and show a mode of stromal closure that relies on whole tissue deformations, cell migration and matrix deposition.
- Mahmut Selman Sakar
- , Jeroen Eyckmans
- & Christopher S. Chen
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Article
| Open AccessLocal 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions
Little is known about how the physical properties of three dimensional (3D) extracellular matrices modulate cell adhesion dynamics. Here Doyle et al.generate 3D collagen gels of varying microarchitecture and quantify the effect on adhesion dynamics and cell motility.
- Andrew D. Doyle
- , Nicole Carvajal
- & Kenneth M. Yamada
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Article
| Open AccessA synthetic hydrogel for the high-throughput study of cell–ECM interactions
Multiple extracellular matrix parameters influence cellular behaviour, but it is difficult to dissect their cooperative contributions. Here the authors describe a hydrogel system in which ligand density and substrate stiffness can be tuned orthogonally to study the contribution of combinations of these parameters simultaneously.
- Andrew D. Rape
- , Mikhail Zibinsky
- & Sanjay Kumar
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| Open AccessMechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix
Assembly of a collagen extracellular matrix requires the presence of fibronectin, but the mechanisms that direct this assembly are not known. Here the authors show that collagen I uses relaxed fibronectin fibrils as a template for assembly, and in turn shield fibronectin fibrils from force-mediated stretching.
- Kristopher E. Kubow
- , Radmila Vukmirovic
- & Viola Vogel
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Adaptive rheology and ordering of cell cytoskeleton govern matrix rigidity sensing
Adherent cells actively probe the rigidity of their substrates. Guptaet al. show that actin cytoskeleton rheology transitions from fluid to solid with increased substrate stiffness along with an isotropic to nematic ordering, implicating the remodelling of the whole actin network in rigidity sensing.
- Mukund Gupta
- , Bibhu Ranjan Sarangi
- & Benoît Ladoux