A discrete interface in matrix stiffness creates an oscillatory pattern of endothelial monolayer disruption

VanderBurgh, Jacob A.; Potharazu, Archit V.; Schwager, Samantha C.; Reinhart‐King, Cynthia A.

doi:10.1242/jcs.244533

Cited by 3 publications

(3 citation statements)

References 54 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also studied how local changes in the substrate stiffness affect the propagation of forces in the epithelium. Stiffness interfaces have been shown to affect the integrity of endothelial monolayers and impact their behavior over a distance of more than a hundred micrometers [57]. Similarly, we found that the cell displacement was affected near p 0 even if the stiffness interface was at a distance of 80 µm.…”

Section: Discussionsupporting

confidence: 66%

The effect of substrate stiffness on tensile force transduction in the epithelial monolayers

Tervonen

Korpela

Nymark

et al. 2021

Preprint

View full text Add to dashboard Cite

In recent years, the importance of mechanical signaling and the cellular mechanical microenvironment in affecting cellular behavior has been widely accepted. Cells in epithelial monolayers are mechanically connected to each other and the underlying extracellular matrix (ECM), forming a highly connected mechanical system subjected to various mechanical cues from their environment, such as the ECM stiffness. Changes in the ECM stiffness have been linked to many pathologies, including tumor formation. However, our understanding of how ECM stiffness and its heterogeneities affect the transduction of mechanical forces in epithelial monolayers is lacking. To investigate this, we used a combination of experimental and computational methods. The experiments were conducted using epithelial cells cultured on an elastic substrate and applying a mechanical stimulus by moving a single cell by micromanipulation. To replicate our experiments computationally and quantify the forces transduced in the epithelium, we developed a new model that described the mechanics of both the cells and the substrate. Our model further enabled the simulations with local stiffness heterogeneities. We found the substrate stiffness to distinctly affect the force transduction as well as the cellular movement and deformation following an external force. Also, we found that local changes in the stiffness can alter the cells' response to external forces over long distances. Our results suggest that this long-range signaling of the substrate stiffness depends on the cells' ability to resist deformation. Furthermore, we found that the cell's elasticity in the apico-basal direction provides a level of detachment between the apical cell-cell junctions and the basal focal adhesions. Our simulation results show potential for increased ECM stiffness, e.g. due to a tumor, to modulate mechanical signaling between cells also outside the stiff region. Furthermore, the developed model provides a good platform for future studies on the interactions between epithelial monolayers and elastic substrates.

show abstract

Section: Discussionsupporting

confidence: 66%

The effect of substrate stiffness on tensile force transduction in the epithelial monolayers

Tervonen

Korpela

Nymark

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…While it is possible to produce PAA hydrogels with stiffness gradients [ 64 ], they generally have a shallow slope. On the other hand, micropillars have been used to create local stiffness boundaries [ 63 , 65 ]. However, in this method the range of possible substrate displacement is limited, and the discrete nature of the substrate affects the cell adhesions [ 49 ].…”

Section: Resultsmentioning

confidence: 99%

“…The material interface and thus the stiffness changes situated 20–80 m, from the manipulated cell. Stiffness interfaces and gradients, for example between healthy and tumor stroma, have been shown to affect the integrity of endothelial monolayers and impact their behavior over distances of more than a hundred micrometers [ 65 ]. Similarly, we found that the cell displacement was affected, even if the stiffness interface was 80 m away from the manipulated cell.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Substrate Stiffness on Elastic Force Transmission in the Epithelial Monolayers over Short Timescales

et al. 2023

View full text Add to dashboard Cite

Purpose The importance of mechanical forces and microenvironment in guiding cellular behavior has been widely accepted. Together with the extracellular matrix (ECM), epithelial cells form a highly connected mechanical system subjected to various mechanical cues from their environment, such as ECM stiffness, and tensile and compressive forces. ECM stiffness has been linked to many pathologies, including tumor formation. However, our understanding of the effect of ECM stiffness and its heterogeneities on rapid force transduction in multicellular systems has not been fully addressed. Methods We used experimental and computational methods. Epithelial cells were cultured on elastic hydrogels with fluorescent nanoparticles. Single cells were moved by a micromanipulator, and epithelium and substrate deformation were recorded. We developed a computational model to replicate our experiments and quantify the force distribution in the epithelium. Our model further enabled simulations with local stiffness gradients. Results We found that substrate stiffness affects the force transduction and the cellular deformation following an external force. Also, our results indicate that the heterogeneities, e.g., gradients, in the stiffness can substantially influence the strain redistribution in the cell monolayers. Furthermore, we found that the cells’ apico-basal elasticity provides a level of mechanical isolation between the apical cell–cell junctions and the basal focal adhesions. Conclusions Our simulation results show that increased ECM stiffness, e.g., due to a tumor, can mechanically isolate cells and modulate rapid mechanical signaling between cells over distances. Furthermore, the developed model has the potential to facilitate future studies on the interactions between epithelial monolayers and elastic substrates.

show abstract

The influence of microenvironment stiffness on endothelial cell fate: Implication for occurrence and progression of atherosclerosis

Cheng,

Yue,

Zhang

et al. 2023

Life Sciences

View full text Add to dashboard Cite

A discrete interface in matrix stiffness creates an oscillatory pattern of endothelial monolayer disruption

Cited by 3 publications

References 54 publications

The effect of substrate stiffness on tensile force transduction in the epithelial monolayers

The effect of substrate stiffness on tensile force transduction in the epithelial monolayers

The Effect of Substrate Stiffness on Elastic Force Transmission in the Epithelial Monolayers over Short Timescales

The influence of microenvironment stiffness on endothelial cell fate: Implication for occurrence and progression of atherosclerosis

Contact Info

Product

Resources

About