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细胞外基质是否通过弹性波包支持细胞间通讯?

Does the Extracellular Matrix Support Cell-Cell Communication by Elastic Wave Packets?

作者信息

Panchenko Artem Y, Tchaicheeyan Oren, Berinskii Igor E, Lesman Ayelet

机构信息

School of Mechanical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv69978, Israel.

The Center for the Physics and Chemistry of Living Systems, Tel Aviv University, Tel Aviv69978, Israel.

出版信息

ACS Biomater Sci Eng. 2022 Dec 12;8(12):5155-5170. doi: 10.1021/acsbiomaterials.2c01049. Epub 2022 Nov 8.

Abstract

The extracellular matrix (ECM) is a fibrous network supporting biological cells and provides them a medium for interaction. Cells modify the ECM by applying traction forces, and these forces can propagate to long ranges and establish a mechanism of mechanical communication between neighboring cells. Previous studies have mainly focused on analysis of static force transmission across the ECM. In this study, we explore the plausibility of dynamic mechanical interaction, expressed as vibrations or abrupt fluctuations, giving rise to elastic waves propagating along ECM fibers. We use a numerical mass-spring model to simulate the longitudinal and transversal waves propagating along a single ECM fiber and across a 2D random fiber network. The elastic waves are induced by an active contracting cell (signaler) and received by a passive neighboring cell (receiver). We show that dynamic wave propagation may amplify the signal at the receiver end and support up to an order of magnitude stronger mechanical cues and longer-ranged communication relative to static transmission. Also, we report an optimal impulse duration corresponding to the most effective transmission, as well as extreme fast impulses, in which the waves are encaged around the active cell and do not reach the neighboring cell, possibly due to the Anderson localization effect. Finally, we also demonstrate that extracellular fluid viscosity reduces, but still allows, dynamic propagation along embedded ECM fibers. Our results motivate future biological experiments in mechanobiology to investigate, on the one hand, the mechanosensitivity of cells to dynamic forces traveling and guided by the ECM and, on the other hand, the impact of ECM architecture and remodeling on dynamic force transmission and its spectral filtering, dispersion, and decay.

摘要

细胞外基质(ECM)是一种支持生物细胞的纤维网络,并为它们提供相互作用的介质。细胞通过施加牵引力来改变ECM,这些力可以传播到很远的距离,并建立相邻细胞之间的机械通讯机制。以往的研究主要集中在分析跨ECM的静力传递。在本研究中,我们探讨了动态机械相互作用的合理性,这种相互作用表现为振动或突然波动,从而产生沿ECM纤维传播的弹性波。我们使用数值质量-弹簧模型来模拟沿单根ECM纤维以及跨二维随机纤维网络传播的纵向和横向波。弹性波由一个主动收缩的细胞(信号源)产生,并被一个被动的相邻细胞(接收者)接收。我们表明,相对于静态传递,动态波传播可能会在接收端放大信号,并支持强度增强一个数量级以上的机械信号和更远距离的通讯。此外,我们报告了对应于最有效传递的最佳脉冲持续时间,以及极端快速脉冲,在极端快速脉冲中,波被困在活动细胞周围,无法到达相邻细胞,这可能是由于安德森局域化效应。最后,我们还证明,细胞外液粘度会降低,但仍允许沿嵌入的ECM纤维进行动态传播。我们的结果推动了未来力学生物学方面的生物学实验,一方面研究细胞对由ECM传播和引导的动态力的机械敏感性,另一方面研究ECM结构和重塑对动态力传递及其频谱滤波、色散和衰减的影响。

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