Substrates with engineered step changes in rigidity induce traction force polarity and durotaxis.
Substrates with engineered step changes in rigidity induce traction force polarity and durotaxis.
复制标题
DOI：
10.1007/s12195-013-0307-6
复制
发表时间：
2014-03
影响因子：
2.8
通讯作者：
Chen, Christopher S.
中科院分区：
文献类型：
--
作者：
Breckenridge, Mark T.;Desai, Ravi A.;Yang, Michael T.;Fu, Jianping;Chen, Christopher S.
刚性传感在从迁移到增殖和分化的多种细胞功能中起着重要作用。在迁移过程中，据报道，单细胞在称为硬旋转的过程中优先向基底的更刚性区域移动。趋硬性可能有助于伤口愈合和原肠胚形成中的细胞迁移，其中组织硬度的局部梯度已被描述。尽管这种现象对生理学和疾病具有潜在的重要性，但仍不清楚刚性如何指导这些行为以及潜在的细胞和分子机制。为了研究在硬脊膜下旋转过程中细胞牵引力的亚细胞分布和动力学的功能作用，我们开发了一种独特的微加工策略，以产生具有两种不同刚度并置的区域图案化的弹性体微柱阵列。在微柱阵列的刚性边界上初始细胞附着后，观察到NIH 3T3成纤维细胞优先向微柱阵列的刚性区域迁移，指示硬旋转。此外，跨越微柱阵列上的刚性边界桥接两个刚性的细胞在基底的更刚性侧上产生了更强的牵引力，与仅接种在微柱阵列的刚性区域上的细胞产生的力难以区分。总之，我们的研究结果强调了阶跃刚性微柱阵列的实用性，以研究牵引力在刚性感知和硬旋转中的功能作用，这表明细胞可以局部感知基底刚性，以诱导不对称的细胞内牵引力分布，从而促进硬旋转。
Rigidity sensing plays a fundamental role in multiple cell functions ranging from migration, to proliferation and differentiation. During migration, single cells have been reported to preferentially move toward more rigid regions of a substrate in a process termed durotaxis. Durotaxis could contribute to cell migration in wound healing and gastrulation, where local gradients in tissue rigidity have been described. Despite the potential importance of this phenomenon to physiology and disease, it remains unclear how rigidity guides these behaviors and the underlying cellular and molecular mechanisms. To investigate the functional role of subcellular distribution and dynamics of cellular traction forces during durotaxis, we developed a unique microfabrication strategy to generate elastomeric micropost arrays patterned with regions exhibiting two different rigidities juxtaposed next to each other. After initial cell attachment on the rigidity boundary of the micropost array, NIH 3T3 fibroblasts were observed to preferentially migrate toward the rigid region of the micropost array, indicative of durotaxis. Additionally, cells bridging two rigidities across the rigidity boundary on the micropost array developed stronger traction forces on the more rigid side of the substrate indistinguishable from forces generated by cells exclusively seeded on rigid regions of the micropost array. Together, our results highlighted the utility of step-rigidity micropost arrays to investigate the functional role of traction forces in rigidity sensing and durotaxis, suggesting that cells could sense substrate rigidity locally to induce an asymmetrical intracellular traction force distribution to contribute to durotaxis.
登录
查看更多内容
DOI：
10.1083/jcb.200812034
发表时间：
2009-06-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dupin I;Camand E;Etienne-Manneville S
通讯作者：
Etienne-Manneville S
DOI：
10.1039/c1ib00043h
发表时间：
2011-09
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Lopez JI;Kang I;You WK;McDonald DM;Weaver VM
通讯作者：
Weaver VM
DOI：
10.1073/pnas.201201198
发表时间：
2001-09-25
影响因子：
11.1
作者：
Wang, HB;Dembo, M;Wang, YL
通讯作者：
Wang, YL
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert PM;Havenstrite KL;Magnusson KE;Sacco A;Leonardi NA;Kraft P;Nguyen NK;Thrun S;Lutolf MP;Blau HM
通讯作者：
Blau HM