Recursive feedback between matrix dissipation and chemo-mechanical signaling drives oscillatory growth of cancer cell invadopodia.
Recursive feedback between matrix dissipation and chemo-mechanical signaling drives oscillatory growth of cancer cell invadopodia.
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DOI：
10.1016/j.celrep.2021.109047
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发表时间：
2021-04-27
期刊：
影响因子：
8.8
通讯作者：
Shenoy VB
中科院分区：
文献类型：
--
作者：
Gong Z;Wisdom KM;McEvoy E;Chang J;Adebowale K;Price CC;Chaudhuri O;Shenoy VB
已知大多数细胞外基质（ecm）具有耗散性，表现出粘弹性和塑性行为。然而，耗散对细胞运动的影响，特别是三维受限微环境下的机械塑性的影响尚不清楚。在这项研究中，我们通过考虑肌凝蛋白募集、肌动蛋白聚合、基质变形和机械敏感信号通路，建立了侵过体动力学的化学力学模型。侵过体是癌细胞用来促进侵袭的突出结构。我们证明，在重复循环中，通过软化ecm，基质耗散促进了侵入性生长，在此期间，塑性变形通过循环棘轮累积。我们的模型揭示了不同的突出模式，振荡或单调，从聚合相关的延伸和肌球蛋白募集动力学的时间尺度的相互作用中出现。我们的模型预测了肌球蛋白、粘连和rho - rho相关激酶（ROCK）途径被抑制后侵过体动力学的变化。总之，我们的工作强调了基质可塑性在浸润细胞动力学中的作用，可以帮助设计耗散生物材料来调节癌细胞的运动。Gong等人建立了一个化学-力学模型，通过考虑肌球蛋白募集、肌动蛋白聚合和机械敏感信号，来预测基质可塑性对侵过体动力学的影响。实验和模拟结果表明，当伸展时间尺度和肌球蛋白动力学具有可比性时，侵殖细胞会发生振荡，而高基质可塑性有利于这种振荡。
Most extracellular matrices (ECMs) are known to be dissipative, exhibiting viscoelastic and often plastic behaviors. However, the influence of dissipation, in particular mechanical plasticity in 3D confining microenvironments, on cell motility is not clear. In this study, we develop a chemo-mechanical model for dynamics of invadopodia, the protrusive structures that cancer cells use to facilitate invasion, by considering myosin recruitment, actin polymerization, matrix deformation, and mechano-sensitive signaling pathways. We demonstrate that matrix dissipation facilitates invadopodia growth by softening ECMs over repeated cycles, during which plastic deformation accumulates via cyclic ratcheting. Our model reveals that distinct protrusion patterns, oscillatory or monotonic, emerge from the interplay of timescales for polymerization-associated extension and myosin recruitment dynamics. Our model predicts the changes in invadopodia dynamics upon inhibition of myosin, adhesions, and the Rho-Rho-associated kinase (ROCK) pathway. Altogether, our work highlights the role of matrix plasticity in invadopodia dynamics and can help design dissipative biomaterials to modulate cancer cell motility. Gong et al. develop a chemo-mechanical model to predict the impact of matrix plasticity on invadopodia dynamics by considering myosin recruitment, actin polymerization, and mechano-sensitive signaling. The combined experiments and simulations show that invadopodia oscillate when timescales for extension and myosin dynamics are comparable, and high matrix plasticity facilitates the oscillations.
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影响因子：
16.6
作者：
Chaudhuri O;Gu L;Darnell M;Klumpers D;Bencherif SA;Weaver JC;Huebsch N;Mooney DJ
通讯作者：
Mooney DJ
DOI：
10.1038/nrm3112
发表时间：
2011-05
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
41.2
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
通讯作者：
Mooney DJ
影响因子：
3.4
作者：
Chang, Julie;Pang, Emily M.;Chaudhuri, Ovijit
通讯作者：
Chaudhuri, Ovijit
影响因子：
3.4
作者：
Alcaraz, J;Buscemi, L;Navajas, D
通讯作者：
Navajas, D