Using Histologic Image Analysis to Understand Biophysical Regulations of Epithelial Cell Morphology DOI Open Access
Alexandra Bermudez,

Samanta Negrete Muñoz,

Rita A. Blaik

et al.

The Biophysicist, Journal Year: 2023, Volume and Issue: 5(1), P. 1 - 14

Published: Dec. 7, 2023

Epithelial mechanics and mechanobiology have become 2 important research fields in life sciences bioengineering. These investigate how physical factors induced by cell adhesion collective behaviors can directly regulate biologic processes, such as organ development disease progression. Cell thus make exciting biophysics education topics to illustrate fundamental physics principles play a role regulating biology. However, the field currently lacks hands-on activities that engage students learning science outreach programs these topics. One area is of robust modules allow observe features shape connect them principles. Here, we demonstrate workflow engages studying epithelial using commercial histology slides frog skin. We show recently developed artificial intelligence-based image-segmentation tools, easily quantify different morphologic high-throughput manner. Using our workflow, reproduce essential findings mechanics: common gamma distribution normalized aspect ratio jammed epithelia constant between nuclear cellular area. Importantly, because only required instrument for this active module readily available light microscope computer, relatively low cost, well portable. scalable at various levels programs. This highly accessible provides fun engaging way introduce world tissue mechanics.

Language: Английский

How does the tubulin code facilitate directed cell migration? DOI Creative Commons

Miguel Marques Simoes-da-Silva,

Marin Barišić

Biochemical Society Transactions, Journal Year: 2025, Volume and Issue: 53(01)

Published: Feb. 21, 2025

Besides being a component of the cytoskeleton that provides structural integrity to cell, microtubules also serve as tracks for intracellular transport. As building units mitotic spindle, distribute chromosomes during cell division. By distributing organelles, vesicles, and proteins, they play pivotal role in diverse cellular processes, including migration, which reorganize facilitate polarization. Structurally, are built up α/β-tubulin dimers, consist various tubulin isotypes undergo multiple post-translational modifications (PTMs). These PTMs allow differentiate into functional subsets, influencing associated processes. This text explores current understanding roles particularly detyrosination acetylation, their implications human diseases.

Language: Английский

Citations

0
Tumor invasiveness is regulated by the concerted function of APC, formins, and Arp2/3 complex DOI Creative Commons
Lautaro Baró, Rabeah A. Almhassneh, Asifa Islam

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(5), P. 109687 - 109687

Published: April 8, 2024

Tumor cell invasion is the initial step in metastasis, leading cause of death from cancer. Invasion requires protrusive cellular structures that steer migration leader cells emanating tumor mass toward neighboring tissues. Actin central to these processes and therefore prime target drugs known as migrastatics. However, broad effects general actin inhibitors limit their therapeutic use. Here, we delineate roles specific nucleators tuning actin-rich invasive protrusions pinpoint potential pharmacological targets. We subject colorectal cancer spheroids embedded collagen matrix-a preclinical model mirroring solid invasiveness-to pharmacologic and/or genetic treatment arrays assess invasiveness. Our data reveal coordinated yet distinct involvement networks nucleated by adenomatous polyposis coli, formins, actin-related protein 2/3 complex biogenesis maintenance protrusions. These findings may open avenues for better targeted therapies.

Language: Английский

Citations

1
Mechanism of APC truncation involved in colorectal cancer tumorigenesis (Review) DOI Open Access

Tuya Wang,

Jing Fu, Ye Huang

et al.

Oncology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Oct. 15, 2024

Adenomatous polyposis coli (APC) is widely recognized as a heavily mutated gene that suppresses tumor growth in colorectal cancer (CRC). Its mutation considered to be the primary and early event occurs development of CRC. In addition, APC has crucial role inhibiting canonical Wnt signaling pathway. mutations CRC result production shortened products. This impairment β-catenin destruction complexes causes an accumulation active cytoplasm nucleus. these compartments, can bind with DNA-binding proteins transcription factor/lymphoid enhancer-binding factor family, thereby activating Consequently, balance numerous cellular processes disrupted, ultimately driving formation tumors. There growing body evidence indicating prevalent occurrence truncation majority cases. Furthermore, it been observed truncated have activation pathway subsequent loss inhibitory function. review aimed provide overview recent advancements understanding mechanism behind its association onset progression

Language: Английский

Citations

1
Actin Cytoskeleton Polymerization and Focal Adhesion as Important Factors in the Pathomechanism and Potential Targets of Mucopolysaccharidosis Treatment DOI Creative Commons
Lidia Gaffke, Estera Rintz, Karolina Pierzynowska

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(13), P. 1782 - 1782

Published: July 5, 2023

The main approach used in the current therapy of mucopolysaccharidosis (MPS) is to reduce levels glycosaminoglycans (GAGs) cells, deposits considered be cause disease. Previous studies have revealed significant differences expression genes encoding proteins involved many processes, like those related actin filaments, MPS cells. Since regulation filaments essential for intracellular transport specific molecules, process which may affect course MPSs, aim this study was evaluate changes that occur cytoskeleton and focal adhesion cells derived from patients with disease, as well I mouse model, assess whether they could potential therapeutic targets different types. Western-blotting, flow cytometry transcriptomic analyses were employed address these issues. key studied before after treatment, assessed. We also analyzed transcripts whose significantly altered identified expressions changed majority types particularly highly expression. For first time, structure/functions an additional element pathogenesis MPSs. Our results suggest possibility using a target approaches

Language: Английский

Citations

2
A truncation mutant of adenomatous polyposis coli (APC) impairs apical cell extrusion through elevated epithelial tissue tension DOI Creative Commons
Wan Jun Gan, Rabina Giri, Jakob Begun

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 10, 2024

ABSTRACT Tissue tension encompasses the mechanical forces exerted on solid tissues within animal bodies, originating from various sources such as cellular contractility, interactions with neighbouring cells and extracellular matrix. Emerging evidence indicates that an imbalance in tissue can influence structural organisation, homeostasis potentially contribute to disease. For instance, heightened impede apical cell extrusion, leading retention of apoptotic or transformed cells. In this study, we investigate potential role adenomatous polyposis coli (APC) modulating tension. Our findings reveal expression APC truncation mutant elevates epithelial via RhoA/ROCK pathway. This elevation induces morphological alterations hampers extrusion cultured organoids, both which could be mitigated by pharmacologically restoring raises possibility mutations may exert pathogenetic effects altering mechanics.

Language: Английский

Citations

0
A truncation mutant of adenomatous polyposis coli impairs apical cell extrusion through elevated epithelial tissue tension DOI Creative Commons
Wan Jun Gan, Rabina Giri, Jakob Begun

et al.

Cytoskeleton, Journal Year: 2024, Volume and Issue: unknown

Published: July 10, 2024

Abstract Tissue tension encompasses the mechanical forces exerted on solid tissues within animal bodies, originating from various sources such as cellular contractility, interactions with neighboring cells and extracellular matrix. Emerging evidence indicates that an imbalance in can influence structural organization, homeostasis, potentially contribute to disease. For instance, heightened tissue impede apical cell extrusion, leading retention of apoptotic or transformed cells. In this study, we investigate potential role adenomatous polyposis coli (APC) modulating tension. Our findings reveal expression APC truncation mutant elevates epithelial via RhoA/ROCK pathway. This elevation induces morphological alterations hampers extrusion cultured organoids, both which could be mitigated by pharmacologically restoring raises possibility mutations may exert pathogenetic effects altering mechanics.

Language: Английский

Citations

0
Using Histologic Image Analysis to Understand Biophysical Regulations of Epithelial Cell Morphology DOI Open Access
Alexandra Bermudez,

Samanta Negrete Muñoz,

Rita A. Blaik

et al.

The Biophysicist, Journal Year: 2023, Volume and Issue: 5(1), P. 1 - 14

Published: Dec. 7, 2023

Epithelial mechanics and mechanobiology have become 2 important research fields in life sciences bioengineering. These investigate how physical factors induced by cell adhesion collective behaviors can directly regulate biologic processes, such as organ development disease progression. Cell thus make exciting biophysics education topics to illustrate fundamental physics principles play a role regulating biology. However, the field currently lacks hands-on activities that engage students learning science outreach programs these topics. One area is of robust modules allow observe features shape connect them principles. Here, we demonstrate workflow engages studying epithelial using commercial histology slides frog skin. We show recently developed artificial intelligence-based image-segmentation tools, easily quantify different morphologic high-throughput manner. Using our workflow, reproduce essential findings mechanics: common gamma distribution normalized aspect ratio jammed epithelia constant between nuclear cellular area. Importantly, because only required instrument for this active module readily available light microscope computer, relatively low cost, well portable. scalable at various levels programs. This highly accessible provides fun engaging way introduce world tissue mechanics.

Language: Английский

Citations

0