研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

上皮细胞之间的力传导依赖于活跃的耦合和机械结构极化。

Force propagation between epithelial cells depends on active coupling and mechano-structural polarization.

发表日期:2023 Aug 07
作者: Artur Ruppel, Dennis Wörthmüller, Vladimir Misiak, Manasi Kelkar, Irène Wang, Philippe Moreau, Adrien Méry, Jean Révilloud, Guillaume Charras, Giovanni Cappello, Thomas Boudou, Ulrich Sebastian Schwarz, Martial Balland
来源: Cellular & Molecular Immunology

摘要:

细胞生成的力在细胞集合体的大规模行为协调中起着重要作用,尤其是在发育、伤口愈合和癌症过程中。机械信号的传播速度比生化信号更快,但可能产生类似的效应,尤其是在具有强烈细胞间粘附的上皮组织中。然而,缺乏关于力生成细胞、穿越细胞间界面的力传播以及接受细胞的相应的定量描述。为了对这一重要情况进行定量分析,我们在这里提出了一个最小的模型系统,即一个H型模式上的两个上皮细胞("细胞双眼")。在光遗传学上激活细胞收缩的主要调节剂RhoA后,通过牵引力和单层应力显微镜观察接受细胞的机械响应。总体而言,我们发现接受细胞显示出积极的响应,使细胞双眼形成一个一致的单元。然而,力的传播和接受细胞的响应也强烈依赖于细胞集合体中的力学结构极化,该极化由细胞与粘附微图案的细胞-基质粘附控制。我们发现,当力学结构极化轴与力传播方向垂直时,接受细胞的响应更强,这类似于被动材料中的泊松效应。最后,我们展示了这些效应也在小样品中起作用。我们的工作表明,细胞组织的组织结构和主动的机械响应对于维持信号强度和产生弹性至关重要,这意味着信号不像黏性系统那样被耗散,而是可以在较远距离传播。© 2023, Ruppel等人。
Cell-generated forces play a major role in coordinating the large-scale behavior of cell assemblies, in particular during development, wound healing and cancer. Mechanical signals propagate faster than biochemical signals, but can have similar effects, especially in epithelial tissues with strong cell-cell adhesion. However, a quantitative description of the transmission chain from force generation in a sender cell, force propagation across cell-cell boundaries, and the concomitant response of receiver cells is missing. For a quantitative analysis of this important situation, here we propose a minimal model system of two epithelial cells on an H-pattern ('cell doublet'). After optogenetically activating RhoA, a major regulator of cell contractility, in the sender cell, we measure the mechanical response of the receiver cell by traction force and monolayer stress microscopies. In general, we find that the receiver cells shows an active response so that the cell doublet forms a coherent unit. However, force propagation and response of the receiver cell also strongly depends on the mechano-structural polarization in the cell assembly, which is controlled by cell-matrix adhesion to the adhesive micropattern. We find that the response of the receiver cell is stronger when the mechano-structural polarization axis is oriented perpendicular to the direction of force propagation, reminiscent of the Poisson effect in passive materials. We finally show that the same effects are at work in small tissues. Our work demonstrates that cellular organization and active mechanical response of a tissue is key to maintain signal strength and leads to the emergence of elasticity, which means that signals are not dissipated like in a viscous system, but can propagate over large distances.© 2023, Ruppel et al.