Nuclear mechanosensing controls MSC osteogenic potential through HDAC epigenetic remodeling DOI Creative Commons
Anouk R. Killaars, Cierra J. Walker, Kristi S. Anseth

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(35), P. 21258 - 21266

Published: Aug. 17, 2020

Significance The extracellular matrix is highly dynamic and presents mechanical signals to the residing cells maintain tissue homeostasis. Recently, nucleus has been implicated be a direct mechanosensor, dysregulation of nuclear mechanosensing might involved in several diseases, including bone degeneration. To better understand mechanisms behind remodeling epigenetic landscape through mechanosensing, we utilize an innovative photostiffening hydrogel platform manipulate human mesenchymal stem cells. Our results reveal that disruption up-regulates histone deacetylases prevents response as well osteogenic fate determination. Interestingly, see similar defective from patients with osteoarthritis, indicating this cellular mechanism likely relevant bone-related diseases.

Language: Английский

Integrins as biomechanical sensors of the microenvironment DOI
Zanetta Kechagia, Johanna Ivaska, Pere Roca‐Cusachs

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(8), P. 457 - 473

Published: June 10, 2019

Language: Английский

Citations

1030

Role of Extracellular Matrix in Development and Cancer Progression DOI Open Access
Cameron Walker,

Elijah Mojares,

Armando E. del Río Hernández

et al.

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(10), P. 3028 - 3028

Published: Oct. 4, 2018

The immense diversity of extracellular matrix (ECM) proteins confers distinct biochemical and biophysical properties that influence cell phenotype. ECM is highly dynamic as it constantly deposited, remodelled, degraded during development until maturity to maintain tissue homeostasis. ECM’s composition organization are spatiotemporally regulated control behaviour differentiation, but dysregulation dynamics leads the diseases such cancer. chemical cues presented by have been appreciated key drivers for both cancer progression. However, mechanical forces present due largely ignored recently recognized play critical roles in disease progression malignant behaviour. Here, we review ways which microenvironment regulation phenotype stages human

Language: Английский

Citations

955

Crosstalk between mechanotransduction and metabolism DOI
Patrizia Romani, Lorea Valcárcel-Jiménez, Christian Frezza

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 22(1), P. 22 - 38

Published: Nov. 13, 2020

Language: Английский

Citations

299

High‐Aspect‐Ratio Nanostructured Surfaces as Biological Metamaterials DOI
Stuart G. Higgins, Michele Becce, Alexis Belessiotis‐Richards

et al.

Advanced Materials, Journal Year: 2020, Volume and Issue: 32(9)

Published: Jan. 16, 2020

Abstract Materials patterned with high‐aspect‐ratio nanostructures have features on similar length scales to cellular components. These surfaces are an extreme topography the level and become useful tools for perturbing sensing environment. Motivation comes from ability of deliver cargoes into cells tissues, access intracellular environment, control cell behavior. structures directly perturb cells' sense respond external forces, influencing fate, enabling new mechanistic studies. Through careful design their nanoscale structure, these systems act as biological metamaterials, eliciting unusual responses. While predominantly used interface eukaryotic cells, there is growing interest in nonanimal prokaryotic interfacing. Both experimental theoretical studies attempted develop a understanding observed behaviors, focusing cell–nanostructure interface. This review considers how nanostructured both stimulate systems.

Language: Английский

Citations

209

Mechanobiology of Macrophages: How Physical Factors Coregulate Macrophage Plasticity and Phagocytosis DOI
Nikhil Jain, Jens Moeller, Viola Vogel

et al.

Annual Review of Biomedical Engineering, Journal Year: 2019, Volume and Issue: 21(1), P. 267 - 297

Published: June 4, 2019

In addition to their early-recognized functions in host defense and the clearance of apoptotic cell debris, macrophages play vital roles tissue development, homeostasis, repair. If misregulated, they steer progression many inflammatory diseases. Much progress has been made understanding mechanisms underlying macrophage signaling, transcriptomics, proteomics, under physiological pathological conditions. Yet, detailed that tune circulating monocytes/macrophages tissue-resident polarization, differentiation, specification, functional plasticity remain elusive. We review how physical factors affect phenotype function, including hunt for particles pathogens, as well implications phagocytosis, autophagy, polarization from proinflammatory prohealing phenotype. further discuss this knowledge can be harnessed regenerative medicine design new drugs immune-modulatory drug delivery systems, biomaterials, scaffolds.

Language: Английский

Citations

197

Matrix stiffness induces a tumorigenic phenotype in mammary epithelium through changes in chromatin accessibility DOI
Ryan S. Stowers, Anna Shcherbina, Johnny Israeli

et al.

Nature Biomedical Engineering, Journal Year: 2019, Volume and Issue: 3(12), P. 1009 - 1019

Published: July 8, 2019

Language: Английский

Citations

183

Surface Roughness and Substrate Stiffness Synergize To Drive Cellular Mechanoresponse DOI
Yong Hou, Leixiao Yu, Wenyan Xie

et al.

Nano Letters, Journal Year: 2019, Volume and Issue: 20(1), P. 748 - 757

Published: Dec. 10, 2019

Material surface topographic features have been shown to be crucial for tissue regeneration and treatment of implanted devices. Many biomaterials were investigated with respect the response cells on roughness. However, some conclusions even conflicted each other due unclear interplay substrate elastic as well lack mechanistic studies. Herein, wide-scale roughness gradient hydrogels, integrating from nanoscale microscale controllable stiffness, developed via soft lithography precise morphology. Based this promising platform, we systematically studied mechanosensitive human mesenchymal stem (MSCs) a broad range roughnesses (200 nm 1.2 μm Rq) different stiffnesses. We observed that MSCs responded in stiffness-dependent manner by reorganizing hierarchical structure. Surprisingly, cellular mechanoresponse osteogenesis obviously enhanced very hydrogels (3.8 kPa) high roughness, which was comparable or better than smooth stiff substrates. These findings extend our understanding interactions between biomaterials, highlighting an effective noninvasive approach regulate cell fate synergetic physical cues.

Language: Английский

Citations

176

Innovative Tools for Mechanobiology: Unraveling Outside-In and Inside-Out Mechanotransduction DOI Creative Commons
Danahé Mohammed, Marie Versaevel,

Céline Bruyère

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2019, Volume and Issue: 7

Published: July 16, 2019

Cells and tissues can sense react to the modifications of physico-chemical properties extracellular environment (ECM) through integrin-based adhesion sites adapt their physiological response in a process called mechanotransduction. Due critical localization at cell-ECM interface, transmembrane integrins are mediators bidirectional signaling, playing key role « outside-in » inside-out signal transduction. After presenting basic conceptual fundamentals related field mechanobiology, we review current state-of-the-art technologies that facilitate understanding mechanotransduction signaling pathways. Finally, highlight innovative technological developments help advance our molecular mechanisms involved nuclear

Language: Английский

Citations

148

Multi-domain translation between single-cell imaging and sequencing data using autoencoders DOI Creative Commons
Karren Yang, Anastasiya Belyaeva, Saradha Venkatachalapathy

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Jan. 4, 2021

Abstract The development of single-cell methods for capturing different data modalities including imaging and sequencing has revolutionized our ability to identify heterogeneous cell states. Different provide perspectives on a population cells, their integration is critical studying cellular heterogeneity its function. While various have been proposed integrate modalities, coupling an open challenge. We here present approach integrating vastly by learning probabilistic between the using autoencoders map shared latent space. validate this RNA-seq chromatin images distinct subpopulations human naive CD4+ T-cells that are poised activation. Collectively, provides framework translate cannot yet be measured within same diverse applications in biomedical discovery.

Language: Английский

Citations

128

How Mechanical Forces Shape Plant Organs DOI
Duy-Chi Trinh, Juan Alonso‐Serra, Mariko Asaoka

et al.

Current Biology, Journal Year: 2021, Volume and Issue: 31(3), P. R143 - R159

Published: Feb. 1, 2021

Language: Английский

Citations

119