Neurite outgrowth and branching of PC12 cells on very soft substrates sharply decreases below a threshold of substrate rigidity

被引:168
作者
Leach, Jennie B.
Brown, Xin Q.
Jacot, Jeffrey G.
DiMilla, Paul A.
Wong, Joyce Y.
机构
[1] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA
[2] Northeastern Univ, Dept Chem & Biol Chem, Boston, MA 02115 USA
关键词
D O I
10.1088/1741-2560/4/2/003
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Rationally designed matrices for nerve tissue engineering and encapsulated cell therapies critically rely on a comprehensive understanding of neural response to biochemical as well as biophysical cues. Whereas biochemical cues are established mediators of neuronal behavior (e.g., outgrowth), physical cues such as substrate stiffness have only recently been recognized to influence cell behavior. In this work, we examine the response of PC 12 neurites to substrate stiffness. We quantified and controlled fibronectin density on the substrates and measured multiple neurite behaviors (e.g., growth, branching, neurites per cell, per cent cells expressing neurites) in a large sample population. We found that PC 12 neurons display a threshold response to substrate stiffness. On the softest substrates tested (shear modulus similar to 10 Pa), neurites were relatively few, short in length and unbranched. On stiffer substrates (shear modulus similar to 10(2)similar to 10(4) Pa), neurites were longer and more branched and a greater percentage of cells expressed neurites; significant differences in these measures were not found on substrates with a shear modulus > 10(2) Pa. Based on these data and comparisons with published neurobiology and neuroengineering reports of neurite mechanotransduction, we hypothesize that results from studies of neuronal response to compliant substrates are cell-type dependent and sensitive to ligand density, sample size and the range of stiffness investigated.
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页码:26 / 34
页数:9
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