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

IF 2.3 4区 医学 Q3 BIOPHYSICS
Cellular and molecular bioengineering Pub Date : 2023-07-13 eCollection Date: 2023-12-01 DOI:10.1007/s12195-023-00772-0
Aapo Tervonen, Sanna Korpela, Soile Nymark, Jari Hyttinen, Teemu O Ihalainen
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引用次数: 1

Abstract

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.

Supplementary information: The online version of this article (10.1007/s12195-023-00772-0) contains supplementary material, which is available to authorized users.

Abstract Image

衬底刚度对短时间尺度上外延单层弹性力传输的影响
目的:机械力和微环境在指导细胞行为方面的重要性已被广泛接受。上皮细胞与细胞外基质(ECM)一起形成了一个高度连接的机械系统,受到来自其环境的各种机械暗示的影响,如 ECM 的硬度以及拉伸力和压缩力。ECM 的硬度与许多病理现象有关,包括肿瘤的形成。然而,我们对 ECM 硬度及其异质性对多细胞系统中快速力传导的影响还没有完全了解:我们采用了实验和计算方法。上皮细胞被培养在带有荧光纳米颗粒的弹性水凝胶上。用微型机械手移动单个细胞,记录上皮细胞和基质的变形。我们建立了一个计算模型来复制我们的实验,并量化上皮细胞中的力分布。我们的模型进一步实现了对局部硬度梯度的模拟:结果:我们发现,基底硬度会影响外力作用下的力传导和细胞变形。同时,我们的结果表明,刚度的异质性(如梯度)会对细胞单层中的应变再分布产生重大影响。此外,我们还发现细胞顶端-基底弹性在一定程度上隔离了顶端细胞-细胞连接和基底焦点粘连:我们的模拟结果表明,ECM 刚度的增加(如肿瘤导致的刚度增加)可在机械上隔离细胞,并调节细胞间的快速机械信号传递距离。此外,所开发的模型还有可能促进未来对上皮单层与弹性基底之间相互作用的研究:本文的在线版本(10.1007/s12195-023-00772-0)包含补充材料,经授权的用户可以查阅。
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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
30
审稿时长
>12 weeks
期刊介绍: The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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