Mechanically primed cells transfer memory to fibrous matrices for invasion across environments of distinct stiffness and dimensionality DOI
J. A. Afonso de Almeida,

Jairaj Mathur,

Ye Lim Lee

et al.

Molecular Biology of the Cell, Journal Year: 2023, Volume and Issue: 34(6)

Published: Jan. 25, 2023

Cells sense and migrate across mechanically dissimilar environments throughout development disease progression. However, it remains unclear whether mechanical memory of past empowers cells to navigate new, three-dimensional extracellular matrices. Here, we show that previously primed on stiff, compared with soft, matrices generate a higher level forces remodel collagen fibers promote invasion. This priming advantage persists in dense or stiffened collagen. We explain this memory-dependent, cross-environment cell invasion through lattice-based model wherein stiff-primed cellular minimize energy required for future According our model, transfer their the matrix via alignment tension, remodeled informs Thus, memory-laden overcome mechanosensing softer challenging cell-matrix memory. Consistent predictions, depletion yes-associated protein destabilizes remodeling before release tension laser ablation disable fiber by lysyl-oxidase inhibition, both which disrupt cell-to-matrix hamper These results have implications cancer, fibrosis, aging, where potential may prolonged response.

Language: Английский

Cell–extracellular matrix mechanotransduction in 3D DOI
Aashrith Saraswathibhatla, Dhiraj Indana, Ovijit Chaudhuri

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(7), P. 495 - 516

Published: Feb. 27, 2023

Language: Английский

Citations

309
Extracellular fluid viscosity enhances cell migration and cancer dissemination DOI Creative Commons
Kaustav Bera, Alexander Kiepas, Inês Godet

et al.

Nature, Journal Year: 2022, Volume and Issue: 611(7935), P. 365 - 373

Published: Nov. 2, 2022

Abstract Cells respond to physical stimuli, such as stiffness 1 , fluid shear stress 2 and hydraulic pressure 3,4 . Extracellular viscosity is a key cue that varies under physiological pathological conditions, cancer 5 However, its influence on biology the mechanism by which cells sense changes in are unknown. Here we demonstrate elevated counterintuitively increases motility of various cell types two-dimensional surfaces confinement, dissemination from three-dimensional tumour spheroids. Increased mechanical loading imposed induces an actin-related protein 2/3 (ARP2/3)-complex-dependent dense actin network, enhances Na + /H exchanger (NHE1) polarization through actin-binding partner ezrin. NHE1 promotes swelling increased membrane tension, which, turn, activates transient receptor potential cation vanilloid 4 (TRPV4) mediates calcium influx, leading RHOA-dependent contractility. The coordinated action remodelling/dynamics, NHE1-mediated RHOA-based contractility facilitates enhanced at viscosities. Breast pre-exposed acquire TRPV4-dependent memory transcriptional control Hippo pathway, migration zebrafish, extravasation chick embryos lung colonization mice. Cumulatively, extracellular regulates both short- long-term cellular processes with pathophysiological relevance biology.

Language: Английский

Citations

228
Engineered hydrogels for mechanobiology DOI
Ulrich Blache, Eden M. Ford, Byung Hang Ha

et al.

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: Dec. 15, 2022

Language: Английский

Citations

110
Biomechanical, biophysical and biochemical modulators of cytoskeletal remodelling and emergent stem cell lineage commitment DOI Creative Commons
Vina D. L. Putra, K. Kilian, Melissa L. Knothe Tate

et al.

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Jan. 19, 2023

Abstract Across complex, multi-time and -length scale biological systems, redundancy confers robustness resilience, enabling adaptation increasing survival under dynamic environmental conditions; this review addresses ubiquitous effects of cytoskeletal remodelling, triggered by biomechanical, biophysical biochemical cues, on stem cell mechanoadaptation emergent lineage commitment. The cytoskeleton provides an adaptive structural scaffold to the cell, regulating emergence structure-function relationships during tissue neogenesis, both in prenatal development as well postnatal healing. Identification mapping mechanical cues conducive remodelling may help establish contexts that can be used prospectively translational design specifications target neogenesis for regenerative medicine. In review, we summarize findings context early healing, its relevance guiding commitment targeted regeneration. We highlight how cytoskeleton-targeting chemical agents modulate differentiation govern responses cells’ emerging form function. further methods spatiotemporal visualization measurement properties cells, a function adaptation. Research these areas facilitate translation own healing potential improve materials, therapies, devices

Language: Английский

Citations

47
Hydrogels and Bioprinting in Bone Tissue Engineering: Creating Artificial Stem‐Cell Niches for In Vitro Models DOI Creative Commons
Francesca K. Lewns, Olga Tsigkou, Liam R. Cox

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(52)

Published: April 23, 2023

Advances in bioprinting have enabled the fabrication of complex tissue constructs with high speed and resolution. However, there remains significant structural biological complexity within tissues that is unable to recapitulate. Bone, for example, has a hierarchical organization ranging from molecular whole organ level. Current techniques materials employed imposed limits on scale, speed, resolution can be achieved, rendering technique reproduce hierarchies cell-matrix interactions are observed bone. The shift toward biomimetic approaches bone engineering, where hydrogels provide biophysical biochemical cues encapsulated cells, promising approach enhancing function development vitro modeling. A major focus modeling creating dynamic microenvironmental niches support, stimulate, direct cellular processes formation remodeling. Hydrogels ideal imitating extracellular matrix since they engineered present various whilst allowing bioprinting. Here, recent advances 3D niche conducive engineering models reviewed.

Language: Английский

Citations

45
Mechanical state transitions in the regulation of tissue form and function DOI
Yanlan Mao, Sara A. Wickström

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(8), P. 654 - 670

Published: April 10, 2024

Language: Английский

Citations

27
Self-generated gradients steer collective migration on viscoelastic collagen networks DOI
Andrew G. Clark, Ananyo Maitra, Cécile Jacques

et al.

Nature Materials, Journal Year: 2022, Volume and Issue: 21(10), P. 1200 - 1210

Published: May 30, 2022

Language: Английский

Citations

62
Programming hydrogels to probe spatiotemporal cell biology DOI Creative Commons
Taimoor H. Qazi, Michael R. Blatchley, Matthew D. Davidson

et al.

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(5), P. 678 - 691

Published: April 11, 2022

Language: Английский

Citations

53
Mechanics of the cellular microenvironment as probed by cells in vivo during zebrafish presomitic mesoderm differentiation DOI Creative Commons
Alessandro Mongera, Marie Pochitaloff,

Hannah J. Gustafson

et al.

Nature Materials, Journal Year: 2022, Volume and Issue: 22(1), P. 135 - 143

Published: Dec. 28, 2022

Tissue morphogenesis, homoeostasis and repair require cells to constantly monitor their three-dimensional microenvironment adapt behaviours in response local biochemical mechanical cues. Yet the parameters of cellular probed by vivo remain unclear. Here, we report mechanics that probe situ during zebrafish presomitic mesoderm differentiation. By quantifying both endogenous cell-generated strains tissue mechanics, show individual stiffness associated with deformations supracellular, foam-like architecture. Stress relaxation leads a perceived decreases over time, probing softest regime. We find most parameters, including those cells, vary along anteroposterior axis as mesodermal progenitors differentiate. These findings expand our understanding mechanosensation might aid design advanced scaffolds for engineering applications.

Language: Английский

Citations

50
Targeting VEGF-A/VEGFR2 Y949 Signaling-Mediated Vascular Permeability Alleviates Hypoxic Pulmonary Hypertension DOI Open Access
Weibin Zhou, Keli Liu, Lei Zeng

et al.

Circulation, Journal Year: 2022, Volume and Issue: 146(24), P. 1855 - 1881

Published: Nov. 17, 2022

Pulmonary hypertension (PH) is associated with increased expression of VEGF-A (vascular endothelial growth factor A) and its receptor, VEGFR2 2), but whether how activation signal participates in the pathogenesis PH unclear.VEGF-A/VEGFR2 Y949-dependent vascular leak were investigated lung samples from patients mice exposed to hypoxia. To study their mechanistic roles hypoxic PH, we examined right ventricle systolic pressure, ventricular hypertrophy, pulmonary vasculopathy mutant carrying knock-in phenylalanine that replaced tyrosine at residual 949 (Vefgr2Y949F) conditional deletion Vegfr2 after chronic hypoxia exposure.We show leads excessive both mice, this because an overactivated VEGF-A/VEGFR2 Y949 signaling axis. In context Yes1 c-Src subsequent VE-cadherin phosphorylation cells are involved Y949-induced permeability. Abolishing by Vefgr2Y949F point mutation was sufficient prevent permeability inhibit macrophage infiltration Rac1 smooth muscle under exposure, thereby leading alleviated manifestations, including muscularization distal arterioles, elevated hypertrophy. It important found myeloid macrophages trivial dispensable for hypoxia-induced abnormalities PH. contrast selective blockage signaling, disruption entire promotes development PH.Our results support notion determinant might serve as attractive therapeutic target pathway disease.

Language: Английский

Citations

42