Sensing and Modulation of Invadopodia across a Wide Range of Rigidities
Sensing and Modulation of Invadopodia across a Wide Range of Rigidities
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DOI：
10.1016/j.bpj.2010.12.3733
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发表时间：
2011-02-02
影响因子：
3.4
通讯作者：
Weaver, Alissa M.
中科院分区：
文献类型：
--
作者：
Parekh, Aron;Ruppender, Nazanin S.;Weaver, Alissa M.
最近的研究表明，细胞外基质的刚性调节癌症的侵袭性，包括形成细胞invadopalial突起;然而，相关的机械范围尚不清楚。在这里，我们使用了组织衍生的模型基底膜（BM）和基质基质和合成材料的组合分析，以了解底物刚性如何调节侵袭伪足。膀胱基质-BM（UBM-BM）被发现是具有3-8 MPa的弹性模量的刚性材料，如通过原子力显微镜和低应变拉伸测试所测量的。基质弹性模量类似于低6倍，表明材料更具顺应性。使用跨越kPa-GPa模量的合成底物，我们发现侵袭伪足相关的细胞外基质降解的峰值集中在30 kPa左右，这也对应于侵袭伪足/细胞的峰值。令人惊讶的是，我们在2GPa下观察到侵入伪足数量的另一个峰值以及指示非常高模量的细胞传感的基因表达变化。基于模型基质和BM的测量的弹性模量，我们预期在基质上发现更多的侵入伪足形成，并且这在UBM-BM的基质侧与BM侧上得到验证。这些数据表明，细胞可以感受到大范围的刚性，高达GPa范围。此外，存在侵袭伪足活性的最佳刚性范围，其可能受到BM刚性的限制。
Recent studies have suggested that extracellular matrix rigidity regulates cancer invasiveness, including the formation of cellular invadopalial protrusions; however, the relevant mechanical range is unclear. Here, we used a combined analysis of tissue-derived model basement membrane (BM) and stromal matrices and synthetic materials to understand how substrate rigidity regulates invadopodia. Urinary bladder matrix-BM (UBM-BM) was found to be a rigid material with elastic moduli of 3-8 MPa, as measured by atomic force microscopy and low-strain tensile testing. Stromal elastic moduli were similar to 6-fold lower, indicating a more compliant material. Using synthetic substrates that span kPa-GPa moduli, we found a peak of invadopodia-associated extracellular matrix degradation centered around 30 kPa, which also corresponded to a peak in invadopodia/cell. Surprisingly, we observed another peak in invadopodia numbers at 2 GPa as well as gene expression changes that indicate cellular sensing of very high moduli. Based on the measured elastic moduli of model stroma and BM, we expected to find more invadopodia formation on the stroma, and this was verified on the stromal versus BM side of UBM-BM. These data suggest that cells can sense a wide range of rigidities, up into the GPa range. Furthermore, there is an optimal rigidity range for invadopodia activity that may be limited by BM rigidity.