Cell-induced confinement effects in soft tissue mechanics

Cell-induced confinement effects in soft tissue mechanics
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DOI:
10.1063/5.0047829
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发表时间:
2021-04-14
影响因子:
3.2
通讯作者:
Janmey, Paul A.
Janmey, Paul A.
中科院分区:
物理与天体物理3区
文献类型:
--
作者:
Song, Dawei;Shivers, Jordan L.;Janmey, Paul A.

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组织的力学性质在其正常和病理生理功能中起着关键作用,例如组织发育、老化、损伤和疾病。了解组织力学不仅对设计用于组织工程和药物测试的逼真仿生材料很重要,而且对开发新的诊断技术和医疗干预也很重要。组织是由限制在细胞外基质(ECM)内的细胞组成的异质材料,这两者至少部分地从生物聚合物的网络获得其结构完整性。然而,纯化的重组生物聚合物网络的流变学无法解释组织力学的许多关键方面。值得注意的是,纯化的网络通常会在施加压缩时软化,而许多软组织(如肝脏、脂肪和大脑)在压缩时反而会变硬。虽然连续介质模型可以很容易地捕捉到这种压缩硬化行为,但其基本机制尚未完全了解。在这篇前瞻性的论文中,我们讨论了几个最近提出的微观机制,可以解释压缩硬化的软组织。这些机制包括(I)ECM和体积保持内含物之间的相互作用,其在经受均匀压缩时促进纤维ECM的伸展主导的硬化,(II)ECM与刚性内含物在非均匀压缩下的相互作用,(III)引起细胞和ECM的压缩硬化的其他内部物理约束,以及(IV)压缩力通过堵塞的压缩硬化细胞的传播。我们进一步确定了一些许多开放的问题,在理解软组织力学的结构-功能关系。
The mechanical properties of tissues play a critical role in their normal and pathophysiological functions such as tissue development, aging, injury, and disease. Understanding tissue mechanics is important not only for designing realistic biomimetic materials for tissue engineering and drug testing but also for developing novel diagnostic techniques and medical interventions. Tissues are heterogeneous materials consisting of cells confined within extracellular matrices (ECMs), both of which derive their structural integrity, at least in part, from networks of biopolymers. However, the rheology of purified reconstituted biopolymer networks fails to explain many key aspects of tissue mechanics. Notably, purified networks typically soften under applied compression, whereas many soft tissues like liver, fat, and brain instead stiffen when compressed. While continuum models can readily capture this compression-stiffening behavior, the underlying mechanism is not fully understood. In this perspective paper, we discuss several recently proposed microscopic mechanisms that may explain compression stiffening of soft tissues. These mechanisms include (I) interactions between the ECM and volume-preserving inclusions that promote extension-dominated stiffening of fibrous ECMs when subject to uniform compression, (II) ECM interactions with rigid inclusions under non-uniform compression, (III) other internal physical constraints that cause compression stiffening of cells and ECMs, and (IV) propagation of compressive forces through jammed, compression-stiffening cells. We further identify a few of the many open problems in understanding the structure-function relationship of soft-tissue mechanics.