期刊
CELLULAR AND MOLECULAR BIOENGINEERING
卷 7, 期 1, 页码 26-34出版社
SPRINGER
DOI: 10.1007/s12195-013-0307-6
关键词
Durotaxis; Cell migration; Rigidity sensing; Mechanotransduction; Microfabrication
资金
- National Institutes of Health [EB00262, HL73305, GM74048]
- Penn Institute for Regenerative Medicine
- Nano/Bio Interface Center
- Center for Musculoskeletal Disorders of the University of Pennsylvania
- American Heart Association Postdoctoral Fellowship
- National Science Foundation Fellowship
- Directorate For Engineering [1129611] Funding Source: National Science Foundation
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1149401] Funding Source: National Science Foundation
- Div Of Civil, Mechanical, & Manufact Inn [1129611] Funding Source: National Science Foundation
Rigidity sensing plays a fundamental role in multiple cell functions ranging from migration, to proliferation and differentiation (Engler et al., Cell 126:677-689, 2006; Lo et al., Biophys. J. 79:144-152, 2000; Wells, Hepatology 47:1394-1400, 2008; Zoldan et al., Biomaterials 32:9612-9621, 2011). 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据