3D environment modulates persistent lamin distribution and the biomechanical signature of the nucleus DOI Open Access
Raquel González-Novo, Héctor Zamora‐Carreras,

Ana de Lope-Planelles

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 10, 2023

ABSTRACT The interplay between cells and their surrounding microenvironment drives multiple cellular functions, including migration, proliferation, cell fate transitions. nucleus is a mechanosensitive organelle that adapts external mechanical biochemical signals provided by the environment into nuclear changes with functional consequences for biology. However, morphological of induced 3D extracellular remain unclear. Here, we demonstrated derived from conditions show an aberrant morphology mislocalization lamin B1 periphery. We found actin polymerization protein kinase C (PKC) activity mediate abnormal distribution in conditions-derived cells. Further experiments indicated these altered chromatin compaction, gene transcription functions such as viability migration. By combining biomechanical techniques, force compression single-nucleus analysis atomic microscopy, optical tweezers, super-resolution have determined different behaviour biophysical signature than control Together, our work substantiates novel insights how alters biology promoting consistent chromatin, morphology, distribution, response nucleus.

Language: Английский

Lamins: The backbone of the nucleocytoskeleton interface DOI Creative Commons

Joan M. Sobo,

Nicholas S. Alagna,

Sean X. Sun

et al.

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 86, P. 102313 - 102313

Published: Jan. 22, 2024

Language: Английский

Citations

20
Confined migration induces heterochromatin formation and alters chromatin accessibility DOI Creative Commons
Chieh-Ren Hsia,

Jawuanna McAllister,

Ovais Hasan

et al.

iScience, Journal Year: 2022, Volume and Issue: 25(9), P. 104978 - 104978

Published: Aug. 17, 2022

During migration, cells often squeeze through small constrictions, requiring extensive deformation. We hypothesized that nuclear deformation associated with such confined migration could alter chromatin organization and function. By studying migrating microfluidic devices mimic interstitial spaces in vivo, we found results increased H3K9me3 H3K27me3 heterochromatin marks persist for days. This "confined migration-induced heterochromatin" (CMiH) was distinct from formation during initiation. Confined decreased accessibility at intergenic regions near centromeres telomeres, suggesting spreading existing sites. Consistent the overall decrease accessibility, global transcription migration. Intriguingly, also identified promoter of genes linked to silencing, tumor invasion, DNA damage response. Inhibiting CMiH reduced speed, promotes Together, our findings indicate induces changes regulate cell other functions.

Language: Английский

Citations

58
The Force is Strong with This Epigenome: Chromatin Structure and Mechanobiology DOI Creative Commons
Chieh-Ren Hsia, Daniël P. Melters, Yamini Dalal

et al.

Journal of Molecular Biology, Journal Year: 2023, Volume and Issue: 435(11), P. 168019 - 168019

Published: June 1, 2023

All life forms sense and respond to mechanical stimuli. Throughout evolution, organisms develop diverse mechanosensing mechanotransduction pathways, leading fast sustained mechanoresponses. Memory plasticity characteristics of mechanoresponses are thought be stored in the form epigenetic modifications, including chromatin structure alterations. These context share conserved principles across species, such as lateral inhibition during organogenesis development. However, it remains unclear how mechanisms alter for specific cellular functions, if altered can mechanically affect environment. In this review, we discuss is by environmental forces via an outside-in pathway emerging concept alterations nuclear, cellular, extracellular environments. This bidirectional feedback between cell environment potentially have important physiological implications, centromeric regulation mechanobiology mitosis, or tumor-stroma interactions. Finally, highlight current challenges open questions field provide perspectives future research.

Language: Английский

Citations

24
Chromosome compartmentalization: causes, changes, consequences, and conundrums DOI
Heng Li, Christopher Playter, Priyojit Das

et al.

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: 34(9), P. 707 - 727

Published: Feb. 22, 2024

Language: Английский

Citations

14
Mechanotransduction in stem cells DOI Creative Commons
Carmelo Ferrai, Carsten Schulte

European Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 103(2), P. 151417 - 151417

Published: May 6, 2024

Nowadays, it is an established concept that the capability to reach a specialised cell identity via differentiation, as in case of multi- and pluripotent stem cells, not only determined by biochemical factors, but also physical aspects microenvironment play key role; interpreted through force-based signalling pathway called mechanotransduction. However, intricate ties between elements involved mechanotransduction, such extracellular matrix, glycocalyx, membrane, integrin adhesion complexes, Cadherin-mediated cell/cell adhesion, cytoskeleton, nucleus, are still far from being understood detail. Here we report what currently known about these general their specific interplay context cells. We furthermore merge this overview more comprehensive picture, aims cover whole mechanotransductive cell/microenvironment interface regulation chromatin structure nucleus. Ultimately, with review outline current picture cues epigenetic how processes might contribute dynamics fate.

Language: Английский

Citations

12
Feeling the force from within – new tools and insights into nuclear mechanotransduction DOI Creative Commons
Julien Morival,

Anna Hazelwood,

Jan Lammerding

et al.

Journal of Cell Science, Journal Year: 2025, Volume and Issue: 138(5)

Published: March 1, 2025

The ability of cells to sense and respond mechanical signals is essential for many biological processes that form the basis cell identity, tissue development maintenance. This process, known as mechanotransduction, involves crucial feedback between force biochemical signals, including epigenomic modifications establish transcriptional programs. These programs, in turn, reinforce properties its withstand perturbation. nucleus has long been hypothesized play a key role mechanotransduction due direct exposure forces transmitted through cytoskeleton, receiving cytoplasmic central function gene regulation. However, parsing out specific contributions from those surface cytoplasm remains substantial challenge. In this Review, we examine latest evidence on how regulates both via nuclear envelope (NE) epigenetic machinery elements within interior. We also explore establishing memory, characterized by mechanical, transcriptomic state persists after stimuli cease. Finally, discuss current challenges field present technological advances are poised overcome them.

Language: Английский

Citations

1
Constricted migration is associated with stable 3D genome structure differences in cancer cells DOI Open Access
Rosela Golloshi, Christopher Playter,

Trevor F. Freeman

et al.

EMBO Reports, Journal Year: 2022, Volume and Issue: 23(10)

Published: Aug. 15, 2022

Language: Английский

Citations

25
Loops, topologically associating domains, compartments, and territories are elastic and robust to dramatic nuclear volume swelling DOI Creative Commons
Jacob T. Sanders, Rosela Golloshi, Priyojit Das

et al.

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: March 18, 2022

Layers of genome organization are becoming increasingly better characterized, but less is known about how these structures respond to perturbation or shape changes. Low-salt swelling isolated chromatin fibers nuclei has been used for decades investigate the structural properties chromatin. But, visible changes in appearance have not linked building blocks structure features along sequence. We combine low-salt with genome-wide chromosome conformation capture (Hi-C) and imaging approaches probe effects extension genome-wide. Photoconverted patterns on during expansion contraction indicate that global preserved after dramatic nuclear volume swelling, suggesting a highly elastic topology. Hi-C experiments before, during, show average contact probabilities at short length scales, reflecting local fiber. surprisingly, this large increase volume, there striking maintenance loops, TADs, active inactive compartments, territories. Subtle differences observed, state, protein interactions, location nucleus can affect strongly given maintained under stress. From observations, we propose topology robust fiber isotropic change, elasticity may be beneficial physiological circumstances size volume.

Language: Английский

Citations

18
Rewiring cancer: 3D genome determinants of cancer hallmarks DOI
Maria Elisa Amodeo, Christine E. Eyler,

Sarah E. Johnstone

et al.

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 91, P. 102307 - 102307

Published: Jan. 24, 2025

Language: Английский

Citations

0
At the nucleus of cancer: how the nuclear envelope controls tumor progression DOI Creative Commons
Francesca Paganelli, Alessandro Poli,

Serena Truocchio

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(2)

Published: Jan. 24, 2025

Abstract Historically considered downstream effects of tumorigenesis—arising from changes in DNA content or chromatin organization—nuclear alterations have long been seen as mere prognostic markers within a genome‐centric model cancer. However, recent findings placed the nuclear envelope (NE) at forefront tumor progression, highlighting its active role mediating cellular responses to mechanical forces. Despite significant progress, precise interplay between NE components and cancer progression remains under debate. In this review, we provide comprehensive up‐to‐date overview how composition affect mechanics facilitate malignant transformation, grounded latest molecular functional studies. We also review research that uses advanced technologies, including artificial intelligence, predict malignancy risk treatment outcomes by analyzing morphology. Finally, discuss progress understanding has paved way for mechanotherapy—a promising approach exploits differences cancerous healthy cells. Shifting perspective on diagnostic potential therapeutic targets, calls further investigation into evolving cancer, innovative strategies transform conventional therapies.

Language: Английский

Citations

0